Endothelin-1 affects capsaicin-evoked release of neuropeptides from rat vas deferens

• Published in: European journal of pharmacology 1999-01, Vol.364 (2), p.183-191
• Main Authors: Filippelli, Amelia, Falciani, Maddalena, Piucci, Brunella, Michele D'Amico, D'Agostino, Bruno, Filippelli, Walter, Rossi, Francesco
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bronchodilator Agents - pharmacology; Calcitonin Gene-Related Peptide - pharmacology; Capsaicin; Capsaicin - pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; Endothelin-1; Endothelin-1 - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Isoproterenol - pharmacology; Male; Mammalian male genital system; Morphology. Physiology; Muscle Contraction - drug effects; Neuropeptide release; Neuropeptides - drug effects; Neuropeptides - metabolism; Papaverine - pharmacology; Rats; Rats, Wistar; Sensory neurone; Tetrodotoxin - pharmacology; Vas Deferens - drug effects; Vas Deferens - innervation; Vas Deferens - metabolism; Vas deferens, rat; Vasodilator Agents - pharmacology; Vertebrates: reproduction
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00841-3

Capsaicin-sensitive neurones release a number of neuropeptides, such as substance P, neurokinin A, somatostatin and calcitonin gene-related peptide (CGRP), which exert a number of effects on smooth muscle tissues. Endothelin-1 was thought to potentiate the capsaicin-evoked release of neuropeptides from sensory neurones of the rat. We have investigated the neuromodulatory effects of endothelin-1 on capsaicin-induced release of neurotransmitters from rat vas deferens. Capsaicin and human α calcitonin gene-related peptide (human αCGRP) reduced the rat vas deferens twitch responses induced by electrical field stimulation. Human β calcitonin gene-related peptide-(8–37) [human βCGRP-(8–37)] (1 μM), a selective αCGRP receptor antagonist, antagonized the inhibitory effects of both drugs. Endothelin-1 concentration dependently evoked an increase in basal tone of the musculature and potentiated the amplitude of the electrically stimulated responses, blocking inhibitory effects of capsaicin but not of human αCGRP. Moreover, endothelin-1 did not markedly change the inhibitory effects of papaverine (0.1–100 μM) or isoprenaline (1 nM–100 μM) on responses to electrical field stimulation. FR 139317 [( N, N-hexamethylene) carbamoyl-Leu- d-Trp( N-Me)- d-2-Pya], a selective endothelin ET A receptor antagonist, administered 30 min before endothelin-1 restored the capsaicin effects whereas BQ 788 [Dmpc-γ-MeLeu- d-Trp-(1-methoxycarbonyl)- d-Nle], a selective endothelin ET B receptor antagonist, was completely ineffective. The endothelin-1-induced block of the capsaicin effect was resistant to tetrodotoxin (1 μM) and 30-min pre-treatment with MEN 10.627 (cyclo[(Met-Asp-Trp-Phe-Dap-Leu) cyclo (2β–5β)]), a selective tachykinin NK 2 receptor antagonist, did not abolish the endothelin-1 effect on the inhibitory response to capsaicin. These results suggest that endothelin-1 selectively inhibits the capsaicin-induced release of neurotransmitters from rat vas deferens and these effects are mediated via endothelin ET A receptors but not by tachykinin release.