Calcitonin gene-related peptide (CGRP) inhibits contractions of the prostatic stroma of the rat but not the guinea-pig

• Published in: Regulatory peptides Vol. 91; no. 1; pp. 63 - 73
• Main Authors: Ventura, Sabatino, Lau, Winnie A.K, Buljubasich, Sretna, Pennefather, Jocelyn N
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 28.07.2000; Amsterdam Elsevier
• Subjects: Adrenomedullin; Amylin; Amyloid - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Anti-Ulcer Agents - pharmacology; Biological and medical sciences; Calcitonin Gene-Related Peptide - agonists; Calcitonin Gene-Related Peptide - pharmacology; Captopril - pharmacology; CGRP receptors; Dose-Response Relationship, Drug; Electrophysiology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glyburide - pharmacology; Glycopeptides - pharmacology; Guinea Pigs; Human CGRP (8–37); Humans; Hypoglycemic Agents - pharmacology; Immunohistochemistry; Islet Amyloid Polypeptide; Leucine - analogs & derivatives; Leucine - pharmacology; Male; Mammalian male genital system; Morphology. Physiology; NG-Nitroarginine Methyl Ester - pharmacology; Norepinephrine - pharmacology; Peptides - pharmacology; Prostate; Prostate - drug effects; Prostate - innervation; Protease Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; Smooth muscle; Time Factors; Tyrosine 3-Monooxygenase - metabolism; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology; Vertebrates: reproduction; Adrenomedullin; Smooth muscle; Human CGRP (8–37); CGRP receptors; Prostate; Amylin; Rat; Rodentia; Calcitonine gene related peptide; Neuropeptide; Vertebrata; Mammalia; Guinea pig; Peptidergic receptor; Mechanism of action; Urogenital system
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/S0167-0115(00)00118-X

This study investigated the presence and effects of calcitonin gene-related peptide (CGRP) within the rat and guinea-pig prostate glands. Immunohistochemical studies demonstrated that CGRP immunoreactive nerve fibres are sparsely distributed throughout the prostatic fibromuscular stroma in both species. These CGRP immunopositive nerve fibres shared a similar distribution profile but were not colocalized with tyrosine hydroxylase immunopositive nerve fibres which also innervate the prostatic stroma of these species. Nerve terminals within rat and guinea-pig prostatic tissues were electrically field stimulated (60 V, 0.5 ms, 10 Hz, 20 pulses every 60 s). In guinea-pig preparations, application of human α-CGRP, rat adrenomedullin or rat amylin (0.1 nM–1 μM) had no effect on responses to field stimulation. In contrast, both rat and human α-CGRP (10 pM–300 nM), rat adrenomedullin (0.3 nM–1 μM) and rat amylin (3 nM–1 μM) concentration-dependently inhibited electrically evoked contractile responses in the rat prostate. The relative order of potency was rat α-CGRP=human α-CGRP>rat adrenomedullin>rat amylin. The inhibition by rat α-CGRP of field stimulation-induced contractions in the rat prostate was competitively antagonized by human CGRP (8–37) (1, 3 and 10 μM) with a pA 2 of 6.20±0.13. Rat α-CGRP (10 nM) attenuated contractile responses of the rat prostate to exogenously added noradrenaline (1–100 μM). Inhibitory concentration–response curves to rat α-CGRP in rat prostates were unaffected by preincubation in either glibenclamide (10–100 μM), N-nitro- l-arginine methyl ester ( l-NAME) (10 μM), bestatin (10 μM), captopril (10 μM) or phosphoramidon (3 μM). Our results indicate that CGRP-induced inhibition of electrically evoked contractions in the rat prostate occurs through activation of postjunctional CGRP 2 receptors which act independently of a K ATP channel or nitrergic mechanisms. Degradation of rat α-CGRP via peptidases does not appear to occur in the rat prostate.