Relaxant effects of pituitary adenylate cyclase activating polypeptide (PACAP) on epithelium-intact and -denuded guinea-pig trachea: a comparison with vasoactive intestinal peptide (VIP).
The effect of pituitary adenylate cyclase activating peptide (PACAP 1-27) was examined on epithelium-intact and -denuded guinea-pig tracheal strips (GPT) and compared to vasoactive intestinal peptide (VIP) and salbutamol. PACAP (10(-11)-10(-8) moles) induced dose-dependent relaxations of the basal tone of both epithelium-intact and -denuded GPT. PACAP was approximately three times less potent than either VIP or salbutamol in relaxing epithelium-intact GPT. The relaxant effects of both peptides and salbutamol were markedly attenuated following removal of the epithelial layer. L-NAME (10(-4) M), a nitric oxide synthase inhibitor, did not affect the responses induced by either PACAP or VIP demonstrating that the relaxant effect is independent of nitric oxide synthesis. Phosphoramidon (5 x 10(-6) M) potentiated the relaxant responses of epithelium-intact GPT to both PACAP and VIP but did not affect the responses of epithelium-denuded GPT. PACAP and VIP also induced relaxations of the guinea-pig upper bronchus. In addition, PACAP (10(-6) M), as well as VIP, significantly inhibited the release of TxB2 induced by LTD4 (10(-7) M) from chopped guinea-pig lung suggesting that this newly isolated peptide, which has 68% homology with VIP, may possess anti-inflammatory action in the lung.
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Canada.
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Conroy
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St-Pierre
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Sirois
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017998:Leukotriene D4 / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013929:Thromboxane B2 / Q000378:metabolism; D014132:Trachea / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D013929:Thromboxane B2; D017998:Leukotriene D4; D001120:Arginine; D000420:Albuterol; D019331:NG-Nitroarginine Methyl Ester