Age and castration modulate the inhibitory action of neuropeptide Y on neurotransmission In the rat vas deferens

doi:10.1016/0014-2999(91)90723-4

European Journal of Pharmacology

Volume 203, Issue 2, 15 October 1991, Pages 267-274

https://doi.org/10.1016/0014-2999(91)90723-4 Get rights and content

Abstract

The potency of neuropeptide Y (NPY) to inhibit the electrically induced contractions of the epididymal half of the vas deferens diminishes markedly with age, being at least 20 times lower in the adult than in the 26-day-old rat. Castration sensitizes the epididymal segment to NPY in a testosterone-reversible manner. [Pro³⁴]NPY was 3 times less potent than NPY in prepubertal rats and inactive in castrated adults, while NPY-(13–36) had no effect in either group. In the prostatic half, NPY and its analogs were active in rats from all ages studied; the order of potency being NPY > [Pro³⁴]NPY > NPY-(13–36). The sensitivity of the prostatic segment from adult rats to NPY was unchanged by castration or testosterone replacement therapy. The NPY content of the ductus increases during development being higher in the prostatic than in the epididymal half at all ages studied. Castration decreases the peptide content in the two segments and the effect is prevented by testosterone administration. The present investigation demonstrated that the effect of NPY on vas deferens neurotransmission is subject to regulation by sex steroids, which affects differently the response of the two segments of the ductus.

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Additionally, inhibiting effects of neuropeptide Y on contractions of the epididymis part of the spermatic duct were evident. In contrast, this effect was not observed in the prostate part of the spermatic duct (Bitran et al., 1991). Regarding innervation density, rats also display reduced amounts of nerve fibers in the skeletal muscles of the pubococcygeus muscle (Alvarado et al., 2013).
Small ruminants are often presumed to be at a higher risk of developing obstructive urolithiasis after early castration. However, the underlying pathophysiology and histological correlation of this assumption is unknown. This study examines the neuropeptide distribution of the lower urinary tract in male lambs in respect to castration status or a recent history of obstructive urolithiasis.
Various tissue samples were taken and examined. The sample consisted of 34 male lambs, aged six months (n = 11 early and n = 11 late castration; n = 12 intact), and 8 rams that had undergone necropsy due to fatal outcome after obstructive urolithiasis. Immunohistochemical stainings for substance P (SP), vasoactive intestinal polypeptide (VIP) and neurofilaments (NF) were performed and compared between the groups.
A significant reduction in immunoreactive signals of SP, VIP and NF was evident in the urolithiasis group (SP and NF: P < 0.0001; VIP: P = 0.02).
The results of immunohistochemistry suggest that castration had no effect on the content of neuropeptides, as well as the innervation density of the urethra in the male lambs. In the case of.
obstructive urolithiasis, the pattern of neuropeptide distribution was severely disturbed and cell damage lead to a reduction in detectable periurethral bundles of nerve fibers. The severe tissue damage was assumed to have a negative impact on the outcome of treatment, leading to complications such as urethral strictures. These, in turn, often result in relapses.
Vas deferens neuro-effector junction: From kymographic tracings to structural biology principles
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Citation Excerpt :
Bitran et al. (1991) reported that the peptide potency to block the tissue contractions elicited by nerve-evoked stimulation was circa 20 nM; the inhibition; in agreement with Huidobro-Toro et al. (1985), was more marked in the prostatic end of the vas deferens. The inhibition is sensitized by reserpine treatment, particularly in the prostatic end of the rat tissue (Huidobro-Toro, 1985) and is dependent on animal age and testosterone, since in castrated rats the effect is reduced (Bitran et al., 1991). The presynaptic modulatory effect of NPY is due to inhibition of NE release via a cAMP independent mechanism (Bitran et al., 1996); no studies have been conducted at present to assess whether NPY also affects ATP release from this tissue.
The vas deferens is a simple bioassay widely used to study the physiology of sympathetic neurotransmission and the pharmacodynamics of adrenergic drugs. The role of ATP as a sympathetic co-transmitter has gained increasing attention and furthered our understanding of its role in sympathetic reflexes. In addition, new information has emerged on the mechanisms underlying the storage and release of ATP. Both noradrenaline and ATP concur to elicit the tissue smooth muscle contractions following sympathetic reflexes or electrical field stimulation of the sympathetic nerve terminals. ATP and adenosine (its metabolic byproduct) are powerful presynaptic regulators of co-transmitter actions. In addition, neuropeptide Y, the third member of the sympathetic triad, is an endogenous modulator. The peptide plus ATP and/or adenosine play a significant role as sympathetic modulators of transmitter's release. This review focuses on the physiological principles that govern sympathetic co-transmitter activity, with special interest in defining the motor role of ATP. In addition, we intended to review the recent structural biology findings related to the topology of the P2X1R based on the crystallized P2X4 receptor from Danio rerio, or the crystallized adenosine A2A receptor as a member of the G protein coupled family of receptors as prototype neuro modulators. This review also covers structural elements of ectonucleotidases, since some members are found in the vas deferens neuro-effector junction. The allosteric principles that apply to purinoceptors are also reviewed highlighting concepts derived from receptor theory at the light of the current available structural elements. Finally, we discuss clinical applications of these concepts.
Plasticity of pelvic autonomic ganglia and urogenital innervation
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Pelvic ganglia contain a mixture of sympathetic and parasympathetic neurons and provide most of the motor innervation of the urogenital organs. They show a remarkable sensitivity to androgens and estrogens, which impacts on their development into sexually dimorphic structures and provide an array of mechanisms by which plasticity of these neurons can occur during puberty and adulthood. The structure of pelvic ganglia varies widely among species, ranging from rodents, which have a pair of large ganglia, to humans, in whom pelvic ganglion neurons are distributed in a large, complex plexus. This plexus is frequently injured during pelvic surgical procedures, yet strategies for its repair have yet to be developed. Advances in this area will come from a better understanding of the effects of injury on the cellular signaling process in pelvic neurons and also the role of neurotrophic factors during development, maintenance, and repair of these axons.
Maturational and maintenance effects of testosterone on terminal axon density and neuropeptide expression in the rat vas deferens
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Testosterone causes growth of many pelvic ganglion cells at puberty and their maintenance during adulthood. Here we have focused on two populations of pelvic ganglion cells that project to the rat vas deferens: noradrenergic neurons that innervate the smooth muscle and synthesize neuropeptide Y, and cholinergic neurons that primarily innervate the mucosa and contain vasoactive intestinal peptide. We have assessed the muscle innervation after pre- or postpubertal castration, using immunohistochemistry to determine axon density and radioimmunoassay to quantify levels of neuropeptides in tissue extracts.
Our results show that androgen deprivation in each period causes substantial effects. Noradrenergic axons in the muscle increase in density after castration, partly due to organ size being smaller than age-matched controls. However, when corrected for target size, there is an overall decrease in total number of axons. This implies that androgen exposure at puberty has a direct effect on neurons to ensure that the adult pattern of innervation is attained, and that this is not simply by matching terminal field to target size. Similar effects of pre- and postpubertal castration imply that continued exposure to testosterone is necessary to maintain normal target innervation. Castration in both time periods increased the density of axons containing vasoactive intestinal peptide, however the effects of castration on the total number of these axons in the muscle were more variable. The concentration of vasoactive intestinal peptide increased substantially following either pre- or postpubertal castration although absolute amounts per vas deferens were decreased. Effects on neuropeptide Y concentration were less pronounced but the total amount per vas deferens was decreased after pre- or postpubertal castration.
Our study shows that the action of testosterone (or a metabolite) on a pelvic ganglion cell soma is likely to reflect a change in its terminal field, but that these effects are not mediated simply by testosterone influencing the size of its target organ.
Pharmacological techniques for the in vitro study of the vas deferens
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Migraine, but not subarachnoid hemorrhage, is associated with differentially increased NPY-like immunoreactivity in the CSF
2000, Journal of the Neurological Sciences
To test whether migraine and subarachnoid hemorrhage (SAH) are associated with increased sympathetic tone, we compared the neuropeptide Y-like (NPY-LI) and chromogranin A-like immunoreactivities (LI) of cerebrospinal fluid (CSF) from migraneurs and SAH patients with those from control subjects. Increased sympathetic tone was expected to produce higher co-release of these co-stored peptides and concordant changes in their CSF levels. In addition, we investigated a possible disturbed nitric oxide homeostasis by measuring CSF nitrites (NO). More than 70% of CSF NPY-LI corresponded to the chromatographic peak (HPLC) for the intact molecule in all three groups. Migraneurs had 64% higher CSF NPY-LI, but no significant difference in CSF chromogranin A-LI, as compared to controls. In contrast, SAH patients had 74% less CSF chromogranin A-LI and a trend to lower NPY-LI, as compared to controls. No differences in CSF NO were detected among groups. These results argue against an increased sympathetic tone in patients with either migraine or SAH, and suggest that the higher CSF NPY-LI of migraneurs probably originates from central neurons. Furthermore, our findings in SAH patients argue in favor of a decreased sympathetic tone; this could be a homeostatic response to counterbalance vasoconstriction mediated by other mechanisms.

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Age and castration modulate the inhibitory action of neuropeptide Y on neurotransmission In the rat vas deferens

Abstract

Neuropeptides

Peptides

Reg. Pept.

Neuroscience

Dev. Brain Res.

Neurosci. Lett.

Neurosci. Lett.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

J. Auton. Nerv. Syst.

J. Biol. Chem.

Neurochem. Int.

Neurosci. Lett.

Neuroscience

Int. Rev. Cytol.

Reg. Pept.

Changes of norepinephrine levels, tyrosine hydroxylase and dopamine-be-tahydroxylase activitie: after castration and testosterone treatment in vas deferens of adult rats

Biol. Reprod.