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

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.