adrenomedullin and phosphoramidon

Topics: Adrenomedullin; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Coronary Circulation; Endothelin-1; Glycopeptides; Humans; Lung; Peptides; Rats; Sepsis

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 alpha-CGRP, rat adrenomedullin or rat amylin (0.1 nM-1 microM) had no effect on responses to field stimulation. In contrast, both rat and human alpha-CGRP (10 pM-300 nM), rat adrenomedullin (0.3 nM-1 microM) and rat amylin (3 nM-1 microM) concentration-dependently inhibited electrically evoked contractile responses in the rat prostate. The relative order of potency was rat alpha-CGRP=human alpha-CGRP>rat adrenomedullin>rat amylin. The inhibition by rat alpha-CGRP of field stimulation-induced contractions in the rat prostate was competitively antagonized by human CGRP((8-37)) (1, 3 and 10 microM) with a pA(2) of 6.20+/-0.13. Rat alpha-CGRP (10 nM) attenuated contractile responses of the rat prostate to exogenously added noradrenaline (1-100 microM). Inhibitory concentration-response curves to rat alpha-CGRP in rat prostates were unaffected by preincubation in either glibenclamide (10-100 microM), N-nitro-L-arginine methyl ester (L-NAME) (10 microM), bestatin (10 microM), captopril (10 microM) or phosphoramidon (3 microM). 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 alpha-CGRP via peptidases does not appear to occur in the rat prostate.

Topics: Adrenomedullin; Amyloid; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Ulcer Agents; Calcitonin Gene-Related Peptide; Captopril; Dose-Response Relationship, Drug; Electrophysiology; Enzyme Inhibitors; Glyburide; Glycopeptides; Guinea Pigs; Humans; Hypoglycemic Agents; Immunohistochemistry; Islet Amyloid Polypeptide; Leucine; Male; NG-Nitroarginine Methyl Ester; Norepinephrine; Peptides; Prostate; Protease Inhibitors; Rats; Rats, Sprague-Dawley; Time Factors; Tyrosine 3-Monooxygenase; Vasoconstrictor Agents; Vasodilator Agents