General Pharmacology: The Vascular System
General PapersGABAB Receptors and Opioid Mechanisms Involved in Homotaurine-Induced Analgesia
Introduction
It has been shown in previous works that 3-amino-propanesulfonic acid (homotaurine)—chemically related to the amino acid taurine—exerts, at equiactive doses, an antinociceptive effect in chemical (acetic acid inducing abdominal constriction) and thermal (tail flick and tail immersion) nociceptive tests in rodents. This action is mediated through cholinergic mechanisms and can be antagonized by scopolamine sulfate and methyl nitrate (Ruiz et al., 1991; Serrano et al., 1992). It has also been shown that homotaurine may act as an agonist to GABAA receptors (Curtis and Watkins 1965; Enna and Snyder 1975; Giotti et al., 1983), and as partial agonist to GABAB receptors (Wojcik 1986). Because bicuculline pretreatment did not modify the aforementioned antinociceptive action, an involvement of GABAA receptors in this effect of homotaurine can be ruled out (Serrano et al., 1992). The present work aims to evaluate whether GABAB receptors are involved in homotaurine-induced analgesia, by using CGP 35348 (CGP)—a competitive antagonist to these receptors (Bittiger et al., 1990; Olpe et al., 1990). Because it is known that there are interactions between opioid and GABAergic mechanisms, it seems of interest to study the possible involvement of opioid pathways in the analgesic activity of homotaurine, via the responses to subanalgesic doses of morphine and pretreatment with the antagonist naloxone.
Section snippets
Materials and methods
Male Swiss OF1 mice and Wistar rats (mean weight 23 g and 250 g, respectively) from the breeding colony of the Medical School were used in the abdominal constrictions induced by acetic acid (mice) and tail flick (rats) tests. The animals were kept in a 12-hr light/dark cycle and had free access to food and water. At least 1 week before the experiments they were transferred to the laboratories where room temperature was maintained at 22±1°C. All drugs were dissolved in saline and injected in a
Results
The effects of homotaurine after pretreatment with different doses of the GABAB antagonist in the abdominal constriction test are shown in Fig. 1. CGP 35348 lacked antinociceptive effect but it effectively antagonized the dose-dependent antinociceptive effect of the amino acid which was statistically significant from 55.6 mg/kg upward.
The overall evaluation of results concluded that statistically significant differences existed between the amino acid–treated group and the one pretreated with
Discussion
The results obtained appear to confirm an involvement of GABAB receptor subpopulations in the antinociceptive activity of homotaurine. This appears to be an effect exerted in the CNS, but homotaurine, being a zwitterion, might cross the blood–brain barrier to a limited extent. For this reason, some researchers have used its calcium acetyl derivative (acamprosate) to improve CNS passage (Chabenat et al., 1988; Nalpas et al., 1990). In our experience however, CNS distribution occurs to an extent
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