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NEUROPHARMACOLOGY
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, Sendai, Japan (H.M., H.W., T.H., W.S., T.Saw., S.S.); Division of Biochemical Analysis, Central Laboratory of Medical Sciences, Juntendo University School of Medicine, Tokyo, Japan (T.F.); and Department of Biochemistry, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan (T.Sak.)
Received November 8, 2005; accepted January 3, 2006.
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Abstract |
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-opioid receptors, pretreatment with the -opioid receptor antagonist norbinaltorphimine markedly reduces the antinociceptive response to i.c.v. or i.t. administered endomorphin-2 but not endomorphin-1. These results suggest that endomorphin-2 initially stimulates µ-opioid receptors, which subsequently induce the release of dynorphins that act on -opioid receptors to produce antinociception. The present study was performed in mice to determine whether the release of dynorphins by i.t. administered endomorphin-2 is mediated through µ-opioid receptors to produce antinociception. Intrathecal pretreatment with an antiserum against dynorphin A-(1–17), but not against dynorphin B-(1–13) or 
-neoendorphin, dose-dependently prevented the paw-withdrawal inhibition by endomorphin-2. The pretreatments with these antisera did not affect the endomorphin-1- or [D-Ala2,MePhe4,Gly(ol)5]enkephalin-induced paw-withdrawal inhibition. The attenuation of endomorphin-2-induced antinociception by i.t. pretreatment with an antiserum against dynorphin A-(1–17) or s.c. pretreatment with norbinaltorphimine was blocked dose-dependently by s.c. pretreatment with the µ-opioid receptor antagonist 
-funaltrexamine or the µ1-opioid receptor antagonist naloxonazine at ultra-low doses that are ineffective against µ-opioid receptor agonists. These results suggest that the spinal antinociception induced by endomorphin-2 is mediated through the stimulation of a distinct subtype of µ1-opioid receptor that induces the release of the endogenous -opioid peptide dynorphin A-(1–17) in the spinal cord.
; Goldberg et al., 1998; Gong et al., 1998; Hosohata et al., 1998). Immunoreactivities for these peptides have been localized in many areas of the central nervous system involved in pain processing, including the dorsal horn of the spinal cord, the caudal trigeminal nucleus, and the periaqueductal gray (Martin-Schild et al., 1997, 1998, 1999; Pierce et al., 1998). Some differences have been noted for the distribution of endomorphin-1 and endomorphin-2 in the brain and spinal cord. Endomorphin-1 is more abundant than endomorphin-2 in the brain, whereas endomorphin-2 dominates in the spinal cord (Martin-Schild et al., 1999). Both of these peptides display high affinity and selectivity for the µ-opioid receptor; however, neither endomorphin has an appreciable affinity for 
- or -opioid receptors (Zadina et al., 1997). Distinct pharmacological properties for the endomorphins have been reported in both electrophysiological (Chapman et al., 1997) and behavioral experiments (Stone et al., 1997; Zadina et al., 1997; Goldberg et al., 1998). The antinociception induced by endomorphin-1 and endomorphin-2 given i.t. or i.c.v. is selectively blocked by pretreatment with µ-opioid receptor antagonists, naloxone, or -funaltrexamine (Zadina et al., 1997; Goldberg et al., 1998; Sakurada et al., 1999), indicating that their antinociception is mediated by the stimulation of µ-opioid receptors. Furthermore, pretreatment with the µ1-opioid receptor antagonist naloxonazine attenuates the antinociception induced by i.t. or i.c.v. administered endomorphin-2 but not endomorphin-1, suggesting that endomorphin-2-induced antinociception is mediated by the stimulation of µ1-opioid receptors (Sakurada et al., 1999, 2000a, 2001, 2002).
Although the antinociceptive effects induced by both endomorphin-1 and endomorphin-2 are mediated by the stimulation of µ-opioid receptors, some differences in antinociceptive effects between endomorphin-1 and endomorphin-2 have been noted. The antinociception induced by supraspinally administered endomorphin-2, but not endomorphin-1, is blocked by i.c.v. pretreatment with the -opioid receptor antagonist norbinaltorphimine or an antiserum against dynorphin A-(1–17), suggesting the possibility that endomorphin-2 stimulates a different subtype of µ-opioid receptor, which subsequently induces the release of dynorphins that act on -opioid receptors to produce antinociception (Tseng et al., 2000). The present behavioral pharmacological study was conducted to determine whether the release of dynorphin A-(1–17) by spinally administered endomorphin-2 is mediated through the stimulation of the µ-opioid receptor.
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Materials and Methods |
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Animals. Male ddY mice weighing 22 to 25 g (SLC, Hamamatsu, Japan) were housed in a light- and temperature-controlled room (light on at 9:00 AM and off at 9:00 PM; 23°C). Food and water were available ad libitum. Animals were used only once.
Drugs and Antisera. Endomorphin-1 (Peptide Institute Inc., Osaka, Japan), endomorphin-2 (Peptide Institute Inc.), [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) (Sigma Chemical Co., St. Louis, MO), naloxonazine (RBI, Natick, MA), -funaltrexamine (RBI), norbinaltorphimine (RBI), antiserum against dynorphin A-(1–17) (Phoenix Pharmaceutical Inc., St. Joseph, MO), antiserum against dynorphin B-(1–13) (Bachem, San Carlos, CA), and antiserum against -neoendorphin (Bachem) were used. Endomorphins, DAMGO, and the antisera were dissolved in sterile artificial cerebrospinal fluid containing 7.4 g of NaCl, 0.19 g of KCl, 0.19 g of MgCl2, and 0.14 g of CaCl2 in 1 liter. Naloxonazine, -funaltrexamine, and norbinaltorphimine were dissolved in saline and injected s.c. in a volume of 0.1 ml/10 g b.wt. 24 h before testing.
Assessment of Antinociceptive Response. The antinociceptive response was assessed with the thermal paw-withdrawal test, using an automated tail-flick unit (BM kiki, Tokyo, Japan). Mice were adapted to the testing environment for at least 1 h before any stimulation. Each animal was restrained with a soft cloth to reduce visual stimuli, and a light beam as a noxious radiant heat stimulation was applied to the hind paw. The light beam focused on the plantar surface of the hind paw, and the latency for the paw-withdrawal response against the noxious radiant heat stimulation was measured. The intensity of the noxious radiant heat stimulation was adjusted so that the predrug latency for the paw-withdrawal response was 2.5 to 3.5 s. The antinociceptive effect was expressed as a percentage of the maximum possible effect, which was calculated with the following equation: [(T1 – T0)/(10 – T0)] x 100, where T0 and T1 are the predrug and postdrug latencies for the paw-withdrawal response, respectively. To prevent tissue damage to the paw, the noxious radiant heat stimulation was terminated automatically if the mouse did not lift the paw within 10 s. The measurement of the paw-withdrawal latency was performed by only one individual who was uninformed about the drug treatment for each mouse.
Intrathecal Administration. The i.t. administration was performed according to the procedure described by Hylden and Wilcox (1980) using a 10-µl Hamilton microsyringe with a 29-gauge needle. The injection volumes for opioid peptides and antisera were 2 and 4 µl, respectively.
Statistical Analysis. The data are expressed as the means ± S.E.M for 10 mice. The statistical significance of the differences between groups was assessed with a one-way analysis of variance (ANOVA) followed by either Dunnett's test or the Bonferroni test or a two-way ANOVA followed by the Bonferroni test.
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Results |
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-Funaltrexamine and Norbinaltorphimine on the Antinociception Induced by Intrathecal Administered Endomorphin-1, Endomorphin-2, and DAMGO. Approximately equipotent doses of endomorphin-1, endomorphin-2, and DAMGO were chosen for the studies. Intrathecal injection of endomorphin-1 (5 nmol), endomorphin-2 (5 nmol), and DAMGO (20 pmol) produced 83.8, 80.8, and 72.2% of maximal possible effect at 5, 5, and 10 min after the injection, respectively (Fig. 1). Groups of mice were pretreated s.c. with the selective µ-opioid receptor antagonist -funaltrexamine (40 mg/kg) or the selective -opioid receptor antagonist norbinaltorphimine (10 mg/kg) 24 h before the i.t. injection of endomorphin-1 (5 nmol), endomorphin-2 (5 nmol), or DAMGO (20 pmol). The inhibition of the paw-withdrawal response induced by endomorphin-1, endomorphin-2, and DAMGO was measured 5, 5, and 10 min after the treatment, respectively. The inhibition of the paw-withdrawal response induced by endomorphin-1, endomorphin-2, or DAMGO was completely inhibited by the pretreatment with -funaltrexamine (Fig. 2). On the other hand, the inhibition of the paw-withdrawal response induced by endomorphin-2 was markedly reduced by the pretreatment with norbinaltorphimine, whereas the effects of endomorphin-1 and DAMGO were insensitive to norbinaltorphimine (Fig. 2).
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Effects of Intrathecal Pretreatment with Antisera against Dynorphin A-(1–17), Dynorphin B-(1–13), and -Neoendorphin on the Antinociception Induced by Intrathecal Administered Endomorphin-1, Endomorphin-2, and DAMGO. Groups of mice were pretreated i.t. with antisera (1:50 dilution) against dynorphin A-(1–17), dynorphin B-(1–13), or -neoendorphin for 15, 15, and 10 min before the i.t. injection of endomorphin-1 (5 nmol), endomorphin-2 (5 nmol), and DAMGO (20 pmol), respectively. The inhibition of the paw-withdrawal response induced by endomorphin-1, endomorphin-2, and DAMGO was measured 5, 5, and 10 min after the treatment, respectively. Intrathecal pretreatment with an antiserum against dynorphin A-(1–17) attenuated the paw-withdrawal inhibition induced by endomorphin-2 in a dose-dependent manner (Fig. 3). However, the paw-withdrawal inhibition induced by endomorphin-2 was not affected by antisera against dynorphin B-(1–13) or -neoendorphin. The same pretreatment with these antisera did not affect the paw-withdrawal inhibition induced by endomorphin-1 or DAMGO (Fig. 3).
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-Funaltrexamine and Naloxonazine Injected Subcutaneous on the Attenuation of Endomorphin-2-Induced Paw-Withdrawal Inhibition by Subcutaneous Pretreatment with Norbinaltorphimine. Subcutaneous pretreatment with ultra-low doses of -funaltrexamine (0.25–3 mg/kg) or naloxonazine (0.031–2 mg/kg) was ineffective against the paw-withdrawal inhibition induced by endomorphin-2 (5 nmol i.t.) (Table 1). In the following experiments, these ultra-low doses of -funaltrexamine and naloxonazine were used. Groups of mice were pretreated s.c. with norbinaltorphimine (10 mg/kg) in combination with -funaltrexamine (0.25–3 mg/kg) or naloxonazine (0.25–2 mg/kg) 24 h before i.t. treatment with endomorphin-2 (5 nmol). The inhibition of paw-withdrawal response induced by endomorphin-2 was measured 5 min after the treatment. Subcutaneous pretreatment with ultra-low doses of -funaltrexamine at 1.0 to 3.0 mg/kg markedly reduced the attenuation of endomorphin-2-induced paw-withdrawal inhibition by s.c. pretreatment with norbinaltorphimine (Fig. 4). A similar phenomenon was observed after s.c. pretreatment with ultra-low doses of naloxonazine (1–4 mg/kg), which significantly diminished the inhibitory effect of norbinaltorphimine on the antinociception of endomorphin-2 (Fig. 5).
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Effects of -Funaltrexamine and Naloxonazine Injected Subcutaneous on the Attenuation of Endomorphin-2-Induced Paw-Withdrawal Inhibition by Intrathecal Pretreatment with an Antiserum against Dynorphin A-(1–17). Groups of mice, pretreated s.c. with -funaltrexamine (0.25–2.0 mg/kg s.c.) or naloxonazine (0.031–0.5 mg/kg) 24 h earlier, were injected i.t. with an antiserum against dynorphin A-(1–17) (1:50 dilution) 15 min before i.t. treatment with endo-mrophin-2 (5 nmol). The inhibition of the paw-withdrawal response induced by endomorphin-2 was measured 5 min after the treatment. Subcutaneous pretreatment with ultra-low doses of -funaltrexamine at 1 or 2 mg/kg markedly reduced the attenuation of endomorphin-2-induced paw-withdrawal inhibition by i.t. treatment with an antiserum against dynorphin A-(1–17) (Fig. 6). Likewise, s.c. pretreatment with ultra-low doses of naloxonazine from 0.031 to 0.5 mg/kg dose-dependently blocked the attenuation of endomorphin-2-induced paw-withdrawal inhibition by i.t. treatment with an antiserum against dynorphin A-(1–17) (Fig. 7).
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Discussion |
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-funaltrexamine, indicating that the antinociception induced by both endomorphin-1 and endomorphin-2 given spinally is mediated by the stimulation of µ-opioid receptors (Sakurada et al., 2000a, 2001). The finding is consistent with evidence that endomorphin-1 and endomorphin-2 have a high affinity for µ-opioid receptors but have no appreciable affinity for either - or -opioid receptors (Zadina et al., 1997). Naloxonazine irreversibly binds to µ1-opioid receptors and inhibits supraspinal antinociception (Ling et al., 1986; Paul et al., 1989; Pick et al., 1991). Recent behavioral pharmacological studies suggest the presence of µ1-opioid receptors that are sensitive to naloxonazine in spinal and supraspinal sites as assayed with the formalin test, hot-plate test, tail-pressure test, and tail-flick tests (Sato et al., 1999; Sakurada et al., 1999, 2000a,b). Autoradiographic studies show that µ1- and µ2-opioid receptors are localized in spinal and supraspinal structures involved in the modulation of nociception (Moskowitz and Goodman, 1985). Naloxonazine at a dose of 35 mg/kg (s.c.) has been used to selectively block µ1-opioid receptors in mice (Ling et al., 1986). The antinociceptive activity of endomorphin-2, but not endomorphin-1, given i.t. was completely blocked by pretreatment with this dose of naloxonazine (Sakurada et al., 2001), suggesting that spinal antinociception induced by endomorphin-2 and endomorphin-1 is mediated through the µ1-opioid receptor and the µ2-opioid receptor, respectively.
In the receptor binding assay, endomorphin-2 can bind both µ1- and µ2-opioid receptors but shows higher affinity for µ1-opioid receptors than for µ2-opioid receptors (Goldberg et al., 1998). In the mice pretreated s.c. with naloxonazine (35 mg/kg), an irreversible antagonist for µ1-opioid receptor, the dose-response curve of endomorphin-2 injected i.t. for antinociception is shifted to the right in a parallel manner (Sakurada et al., 1999). In contrast, endomorphin-2 given i.t. cannot produce the antinociception, even at higher doses in the mice pretreated s.c. with -funaltrexamine, an irreversible antagonist for both µ1- and µ2-opioid receptors. These findings suggest that, although endomorphin-2 produces the spinal antinociception predominantly mediated through the µ1-opioid receptor, endomorphin-2 can produce the antinociception via the µ2-opioid receptor if the µ1-opioid receptor is occupied.
We found in a recent study that H-Tyr-D-Arg-Phe--Ala-OH (TAPA), a dermorphin tetrapeptide analog, is highly selective for the µ1-opioid receptor (Mizoguchi et al., 2004). More recently, we have demonstrated that the inhibitory effect induced by i.t. administered TAPA against i.t. capsaicin-elicited nociceptive responses is more potent than that against i.t. substance P-elicited nociceptive responses and was almost completely attenuated by s.c. pretreatment with naloxonazine, but not by i.t. coadministration of H-Tyr-D-Pro-Trp-Gly-NH2(D-Pro2 -Tyr-W-MIF-1), the µ2-opioid receptor antagonist (Watanabe et al., 2005), suggesting that TAPA may selectively act at µ1-opioid receptors localized presynaptically on excitatory amino acid- and neuropeptide-containing axon terminals in the dorsal horn (Watanabe et al., 2006). Likewise, antinociception induced by i.t. administered endomorphin-2 on capsaicin-induced nociceptive responses but not substance P-induced nociceptive responses was completely antagonized by s.c. pretreatment with naloxonazine (H. Watanabe, unpublished data). Endomorphin-2-like immunoreactivity is diminished by dorsal rhizotomy or exposure to capsaicin and is colocalized with calcitonin gene-related peptide or substance P (Martin-Schild et al., 1997, 1998; Pierce et al., 1998). Our above results with endomorphin-2 on capsaicin-induced nociceptive responses are in agreement with the findings reported by Martin-Schild et al. (1997, 1998) and Pierce et al. (1998). These results suggest that the release of neurotransmitters from nociceptive primary afferents is regulated by endomorphin-2 in primary afferent terminals through the µ1-opioid receptors.
Prodynorphin produces three main peptides: -neoendorphin, dynorphin A-(1–17), and dynorphin B-(1–13). High levels of dynorphins are found in the brain as well as the dorsal horn of the spinal cord where modulation of nociceptive information occurs (Weber et al., 1982; Slater and Patel, 1983; Tan-No et al., 1997). Because dynorphin family members, such as dynorphin A-(1–17), dynorphin B-(1–13), and -neoendorphin, have a high affinity for the -opioid receptor, dynorphins have been suggested to be the endogenous ligands for -opioid receptors (Chavkin and Goldstein, 1981; Chavkin et al., 1982). Dynorphins have been shown to produce antinociception when administered i.t. (Han and Xie, 1982; Piercey et al., 1982). -Opioid and µ-opioid receptor mRNA is intensely expressed in substance P-containing neurons (Satoh and Minami, 1995). Therefore, - and µ-opioid receptor agonists have been considered to act directly on the primary afferent terminals of substance P-containing neurons to presynaptically modulate the release of substance P (Jessell and Iversen, 1977; Zachariou and Goldstein, 1997). In the present study, we explored the possibility that i.t. administered endomorphin-2-induced antinociception is mediated by the spinal release of dynorphin A-(1–17) via µ-opioid receptors. We found that i.t. pretreatment with an antiserum against dynorphin A-(1–17) or s.c. pretreatment with the -opioid receptor antagonist norbinaltorphimine attenuated the paw-withdrawal inhibition induced by i.t. administered endomorphin-2. However, i.t. pretreatment with an antiserum against dynorphin B-(1–13) or -neoendorphin did not block the endomorphin-2-induced antinociception, indicating that the effect of endomorphin-2 is selective for the release of dynorphin A-(1–17). This view is supported by the previous findings that the antinociception produced by spinally administered endomorphin-2 is attenuated by i.t. pretreatment with an antiserum against dynorphin A-(1–17) or the -opioid receptor antagonist norbinaltorphimine (Ohsawa et al., 2001; Sakurada et al., 2001).
It should be noted that the pharmacological ability of endomorphin-2 to release dynorphin A-(1–17) may be mainly involved in several discrepancies between endomorphin-1 and endomorphin-2 on their pharmacological effects, especially on the rewarding effect and locomotor enhancement. Endomorphin-1 given i.c.v. produces a remarkable rewarding and locomotor-enhancing effect in a dose-dependent manner (Bujdoso et al., 2001b; Narita et al., 2001). In contrast, endomorphin-2 given i.c.v. shows a bell-shaped dose-response curve for the rewarding and locomotor-enhancing effects and prominently produces an aversive rather than rewarding effect (Bujdoso et al., 2001a; Narita et al., 2001). As is well known, the rewarding and locomotor-enhancing effects of µ-opioid receptor agonists are mediated by the disinhibition of mesolimbic and nigrostriatal dopaminergic neurons via the activation of µ-opioid receptors located on the GABAergic neurons in the ventral tegmental area and substantia nigra, respectively (Narita et al., 2001). In the terminal of mesolimbic and nigrostriatal dopaminergic neurons on the nucleus accumbens and striatum, respectively, dynorphinergic neurons are localized to inhibit the release of dopamine. As we found for the spinal antinociception in the present study, unlike endomorphin-1, endomorphin-2 has a characteristic pharmacological ability to release dynorphin A-(1–17). The release of dynorphin A-(1–17) in the nucleus accumbens and striatum may be involved in the lack of the remarkable rewarding effect and locomotor enhancing effect of endomorphin-2. In fact, endomorphin-2 shows a remarkable rewarding effect when dynorphin A-(1–17) is blocked by the use of its antiserum (Narita et al., 2001).
In the present study, s.c. pretreatment with ultra-low doses of -funaltrexamine or naloxonazine that are ineffective against endomorphin-2 surprisingly prevented the attenuation of i.t. administered endomorphin-2-induced antinociception by i.t. pretreatment with an antiserum against dynorphin A-(1–17) or s.c. pretreatment with norbinaltorphimine. These findings suggest that endomorphin-2 preferentially stimulates a distinct µ1-opioid receptor (µ1-opioid receptor subtype-1), which is extremely sensitive to naloxonazine and subsequently induces the release of dynorphin A-(1–17) that acts on -opioid receptors to produce antinociception. However, if the µ1-opioid receptor subtype-1 is occupied by ultra-low doses of naloxonazine or -funaltrexamine, endomorphin-2 should bind to another µ1-opioid receptor (µ1-opioid receptor subtype-2). Therefore, although the component of antinociception induced by i.t. administered endomorphin-2 depends on the release of dynorphin A-(1–17), endomorphin-2-induced antinociception was not affected by the blockade of released dynorphin A-(1–17) after s.c. pretreatment with ultra-low doses of naloxonazine or -funaltrexamine. This finding led us to speculate that, when ultra-low doses of naloxonazine or -funaltrexamine interrupt endomorphin-2 binding to the µ1-opioid receptor subtype-1, which regulates the release of dynorphin A-(1–17) from dynorphinergic neurons that project to primary afferent terminals, endomorphin-2 at primary afferent terminals may act on the µ1-opioid receptor subtype-2, which is not involved in the release of dynorphin A-(1–17) (Fig. 8). Judging from the sensitivity to naloxonazine, we first propose here that there are two subtypes of µ1-opioid receptors that are involved in endomorphin-2-induced antinociception. One, an µ1-opioid receptor subtype-2, is sensitive to -funaltrexamine (40 mg/kg s.c.) and naloxonazine (10–35 mg/kg s.c.) (Sakurada et al., 2000a) and is not involved in the release of dynorphin A-(1–17). The other, an µ1-opioid receptor subtype-1, is involved in the release of dynorphin A-(1–17) acting on -opioid receptors as an additional component of endomorphin-2-induced antinociception and is highly sensitive to both naloxonazine and -funaltrexamine. The present study provides important evidence in the investigation of the spinal neuronal circuit for production of endomorphin-2-induced antinociception.
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In conclusion, endomorphin-2 given spinally produces the antinociception via simulation of multiple µ1-opioid receptors, µ1-opioid receptor subtype-1 and µ1-opioid receptor subtype-2. The µ1-opioid receptor subtype-1, which is extremely sensitive to naloxonazine and -funaltrexamine, may be involved in the additional component of endomorphin-2-induced antinociception, which is mediated through the release of the endogenous -opioid peptide dynorphin A-(1–17).
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Footnotes |
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ABBREVIATIONS: DAMGO, [D-Ala2,MePhe4,Gly(ol)5]enkephalin; ANOVA, analysis of variance; TAPA, H-Tyr-D-Arg-Phe--Ala-OH.
Address correspondence to: Dr. Shinobu Sakurada, Tohoku Pharmaceutical University, Department of Physiology and Anatomy, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. E-mail: s-sakura{at}tohoku-pharm.ac.jp
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References |
|---|
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Bujdoso E, Jaszberenyi M, Tomboly C, Toth G, and Telegdy G (2001a) Behavioral and neuroendocrine actions of endomorphin-2. Peptides 22: 1459–1463.[CrossRef][Medline]
Bujdoso E, Jaszberenyi M, Tomboly C, Toth G, and Telegdy G (2001b) Effects of endomorphin-1 on open-field behavior and on the hypothalamic-pituitary-adrenal system. Endocrine 14: 221–224.[CrossRef][Medline]
Chapman V, Diaz A, and Dickenson AH (1997) Distinct inhibitory effects of spinal endomorphin-1 and endomorphin-2 on evoked dorsal horn neuronal responses in the rat. Br J Pharmacol 122: 1537–1539.[CrossRef][Medline]
Chavkin C and Goldstein A (1981) Specific receptor for the opioid peptide dynorphin: Structure-activity relationships. Proc Natl Acad Sci USA 78: 6543–6547.
Chavkin C, James IF, and Goldstein A (1982) Dynorphin is a specific endogenous ligand for the kappa opioid receptor. Science (Wash DC) 215: 413–415.
Goldberg IE, Rossi GC, Letchworth SR, Mathis JP, Ryan-Moro J, Leventhal L, Su W, Emmel D, Bolan EA, and Pasternak GW (1998) Pharmacological characterization of endomorphin-1 and endomorphin-2 in mouse brain. J Pharmacol Exp Ther 286: 1007–1013.
Gong J, Strong JA, Zhang S, Yue X, DeHaven RN, Daubert JD, Cassel JA, Yu G, Mansson E, and Yu L (1998) Endomorphins fully activate a cloned human mu opioid receptor. FEBS Lett 439: 152–156.[CrossRef][Medline]
Han J-S and Xie C-W (1982) Dynorphin: potent analgesic effect in spinal cord of the rat. Life Sci 31: 1781–1784.[CrossRef][Medline]
Hosohata K, Burkey TH, Alfaro-Lopez J, Varga E, Hruby VJ, Roeske WR, and Yamamura HI (1998) Endomorphin-1 and endomorphin-2 are partial agonists at the human mu-opioid receptor. Eur J Pharmacol 346: 111–114.[CrossRef][Medline]
Hylden JL and Wilcox GL (1980) Intrathecal morphine in mice: a new technique. Eur J Pharmacol 67: 313–316.[CrossRef][Medline]
Jessell TM and Iversen LL (1977) Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature (Lond) 268: 549–551.[CrossRef][Medline]
Ling GS, Simantov R, Clark JA, and Pasternak GW (1986) Naloxonazine action in vivo. Eur J Pharmacol 129: 33–38.[CrossRef][Medline]
Martin-Schild S, Gerall AA, Kastin AJ, and Zadina JE (1998) Endomorphin-2 is an endogenous opioid in primary sensory afferent fibers. Peptides 19: 1783–1789.[CrossRef][Medline]
Martin-Schild S, Gerall AA, Kastin AJ, and Zadina JE (1999) Differential distribution of endomorphin 1- and endomorphin 2-like immunoreactivities in the CNS of the rodent. J Comp Neurol 405: 450–471.[CrossRef][Medline]
Martin-Schild S, Zadina JE, Gerall AA, Vigh S, and Kastin AJ (1997) Localization of endomorphin-2-like immunoreactivity in the rat medulla and spinal cord. Peptides 18: 1641–1649.[CrossRef][Medline]
Mizoguchi H, Yuhki M, Watanabe H, Hayashi T, Sakurada C, Yonezawa A, Sakurada T, and Sakurada S (2004) Differential involvement of µ1-opioid receptors in dermorphin tetrapeptide analogues-induced antinociception. Eur J Pharmacol 486: 19–24.[CrossRef][Medline]
Moskowitz AS and Goodman RR (1985) Autoradiographic distribution of mu1 and mu2 opioid binding in the mouse central nervous system. Brain Res 360: 117–129.[CrossRef][Medline]
Narita M, Ozaki S, Ioka M, Mizoguchi H, Nagase H, Tseng LF, and Suzuki T (2001) Different motivational effects induced by the endogenous µ-opioid receptor ligands endomorphin-1 and -2 in the mouse. Neuroscience 105: 213–218.[CrossRef][Medline]
Ohsawa M, Mizoguchi H, Narita M, Nagase H, Kampine JP, and Tseng LF (2001) Differential antinociception induced by spinally administered endomorphin-1 and endomorphin-2 in the mouse. J Pharmacol Exp Ther 298: 592–597.
Paul D, Bodnar RJ, Gistrak MA, and Pasternak GW (1989) Different µ receptor subtypes mediate spinal and supraspinal analgesia in mice. Eur J Pharmacol 168: 307–314.[CrossRef][Medline]
Pick CG, Paul D, and Pasternak GW (1991) Comparison of naloxonazine and -funaltrexamine antagonism of mu 1 and mu 2 opioid actions. Life Sci 48: 2005–2011.[CrossRef][Medline]
Pierce TL, Grahek MD, and Wessendorf MW (1998) Immunoreactivity for endomorphin-2 occurs in primary afferents in rats and monkey. Neuroreport 9: 385–389.[Medline]
Piercey MF, Varner K, and Schroeder LA (1982) Analgesic activity of intraspinally administered dynorphin and ethylketocyclazocine. Eur J Pharmacol 80: 283–284.[CrossRef][Medline]
Sakurada S, Hayashi T, Yuhki M, Fujimura T, Murayama K, Yonezawa A, Sakurada C, Takeshita M, Sato T, Zadina JE, et al. (2002) Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methoxynaltrexone. Peptides 23: 895–901.[CrossRef][Medline]
Sakurada S, Hayashi T, Yuhki M, Fujimura T, Murayama K, Yonezawa A, Sakurada C, Takeshita M, Zadina JE, Kastin AJ, et al. (2000a) Differential antagonism of endomorphin-1 and endomorphin-2 spinal antinociception by naloxonazine and 3-methoxynaltrexone. Brain Res 881: 1–8.[CrossRef][Medline]
Sakurada S, Hayashi T, Yuhki M, Orito T, Zadina JE, Kastin AJ, Fujimura T, Murayama K, Sakurada C, Sakurada T, et al. (2001) Differential antinociceptive effects induced by intrathecally administered endomorphin-1 and endomorphin-2 in the mouse. Eur J Pharmacol 427: 203–210.[CrossRef][Medline]
Sakurada S, Takeda S, Sato T, Hayashi T, Yuki M, Kutsuwa M, Tan-No K, Sakurada C, Kisara K, and Sakurada T (2000b) Selective antagonism by naloxonazine of antinociception by Tyr-D-Arg-Phe--Ala, a novel dermorphin analogue with high affinity at µ-opioid receptors. Eur J Pharmacol 395: 107–112.[CrossRef][Medline]
Sakurada S, Zadina JE, Kastin AJ, Katsuyama S, Fujimura T, Murayama K, Yuki M, Ueda H, and Sakurada T (1999) Differential involvement of µ-opioid receptor subtypes in endomorphin-1- and -2-induced antinociception. Eur J Pharmacol 372: 25–30.[CrossRef][Medline]
Sato T, Sakurada S, Takahashi N, Sakurada T, Tan-No K, Wako K, and Kisara K (1999) Contribution of spinal µ1-opioid receptors to morphine-induced antinociception. Eur J Pharmacol 369: 183–187.[CrossRef][Medline]
Satoh M and Minami M (1995) Molecular pharmacology of the opioid receptors. Pharmacol Ther 68: 343–364.[CrossRef][Medline]
Slater P and Patel S (1983) Autoradiographic localization of opiate receptors in the rat spinal cord. Eur J Pharmacol 92: 159–160.[CrossRef][Medline]
Stone LS, Fairbanks CA, Laughlin TM, Nguyen HO, Bushy TM, Wessendorf MW, and Wilcox GL (1997) Spinal analgesic actions of the new endogenous opioid peptides endomorphin-1 and -2. Neuroreport 8: 3131–3135.[Medline]
Tan-No K, Terenius L, Silberring J, and Nylander I (1997) Levels of dynorphin peptides in the central nervous system and pituitary gland of the spontaneously hypertensive rat. Neurochem Int 31: 27–32.[CrossRef][Medline]
Tseng LF, Narita M, Suganuma C, Mizoguchi H, Ohsawa M, Nagase H, and Kampine JP (2000) Differential antinociceptive effects of endomorphin-1 and endomorphin-2 in the mouse. J Pharmacol Exp Ther 292: 576–583.
Watanabe H, Nakayama D, Ito K, Watanabe C, Mizoguchi H, Fujimura T, Murayama K, Kawamura S, Sato T, Sakurada C, et al. (2005) A Tyr-W-MIF-1 analog containing D-Pro2 acts as a selective µ2-opioid receptor antagonist in the mouse. J Pharmacol Exp Ther 312: 1075–1081.
Watanabe H, Nakayama D, Yuhki M, Sawai T, Sakurada W, Katsuyama S, Hayashi T, Watanabe C, Mizoguchi H, Fujimura T, et al. (2006) Differential inhibitory effects of µ-opioids on substance P- and capsaicin-induced nociceptive behavior in mice. Peptides, in press.
Weber E, Evans CJ, and Barchas JD (1982) Predominance of the amino-terminal octapeptide fragment of dynorphin in rat brain regions. Nature (Lond) 299: 77–79.[CrossRef][Medline]
Zachariou V and Goldstein BD (1997) Dynorphin-(1–8) inhibits the release of substance P-like immunoreactivity in the spinal cord of rats following a noxious mechanical stimulus. Eur J Pharmacol 323: 159–165.[CrossRef][Medline]
Zadina JE, Hackler L, Ge LJ, and Kastin AJ (1997) A potent and selective endogenous agonist for the mu-opiate receptor. Nature (Lond) 386: 499–502.[CrossRef][Medline]
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