Calcitonin gene-related peptide in noradrenergic transmission in rat hypothalamus.

Abstract

In the present study, we examined the regulatory mechanisms of calcitonin gene-related peptide on norepinephrine release in rat hypothalamus. Calcitonin gene-related peptide inhibited the stimulationevoked norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner, although the peptide did not affect basal release of norepinephrine. The blockade of the o?2-adrenergic receptors by RX 781094 failed to modulate the inhibitory effects of calcitonin gene-related peptide on norepinephrine release. Pretreatment of slices with islet activating protein, a toxin that interferes with the coupling of the inhibitory receptors to adenylate cyclase, did not affect the suppression of norepinephrine release by calcitonin gene-related peptide. However, Bay K 8644, a dihydropyridinesensitive calcium channel agonist, significantly reversed the inhibitory effects of calcitonin gene-related peptide on norepinephrine release. These results show that calcitonin gene-related peptide might inhibit norepinephrine release in rat hypothalamus, partially mediated by interactions with dihydropyridinesensitive Ca 2+ channels but not by interactions with presynaptic « 2 -adrenergic receptors and inhibitory guanosine triphosphate binding proteins. In immunohistochemical studies, it has been shown that CGRP is widely distributed in both the central and peripheral nervous systems.23 The presence of a high level of CGRP immunoreactivity has been demonstrated in the central amydaloid, caudate putamen, spinal trigeminal nucleus and tract, substantia gelatinosa, dorsal horn of spinal cord, hypothalamus, and medulla oblongata containing nucleus tractus solitarii in rats.3 These findings suggest that CGRP might have a crucial role in the regulation of sensory, motor, and autonomic nerve functions. It has been reported that intracerebroventricular administration of CGRP produced a dose-dependent increase in blood pressure and

Functional differences between junctional and extrajunctional adrenergic receptor activation in mammalian ventricle

“…Another possible explanation is the myriad potentiating effects of cotransmitters released from adrenergic terminals within the heart such as CGRP, neuro- peptide-Y, and galanin (1,29). These neuropeptides are known to modulate NE and acetylcholine release (4,12,30,31) and may have a variety of effects on myocardial excitability under normal and pathological conditions. Dispersion of repolarization.…”

“…It is not known whether these single-nucleotide polymorphisms would be associated with disparate responses in repolarization heterogeneity during states of heightened sympathetic tone. Other factors that may contribute to this phenomenon include neuropeptide cotransmitters, which may affect myocardial excitability directly or indirectly (4,12,30,31).…”

Capsaicin in Albino Rats Prevents Contralateral Testis from the Damaging Effects Posed by Ipsilateral Testis That Underwent Torsion

“…It is also reported that CGRP may regulate the electrolyte and fluid secretion in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of the spermatozoa [27]. CGRP further inhibits the release of norepinephrine [28]which was previously reported to be released in excessive amounts in contralateral testis during unilateral testicular torsion [29]. The administration of capsaicin may have further released CGRP and caused dilatation of the vessels thus contributed to the preservation of blood flow to the contralateral testis.…”

Regarding Article “Receptor Activity-Modifying Protein-1 Augments Cerebrovascular Responses to Calcitonin Gene-Related Peptide and Inhibits Angiotensin II-Induced Vascular Dysfunction”

“…In a study we presented previously, the changes in norepinephrine release induced by CGRP was investigated in the rat central nervous system. 2 In an in vitro study, we showed that CGRP inhibited the stimulationevoked norepinephrine release in a dose-dependent manner. It was also demonstrated that a dihydropyridine-sensitive calcium channel agonist, Bay K 8644, significantly reversed the inhibitory effect of CGRP on norepinephrine release, indicating that CGRP might partially interact with dihydropyridine-sensitive calcium channels and modulate intracellular calcium mobilization.…”