The P(2)-purinoceptor antagonist suramin is a competitive antagonist at vasoactive intestinal peptide receptors in the rat gastric fundus.
The P(2)-purinoceptor antagonist, suramin, was used to investigate the possible involvement of adenosine 5'-triphosphate (ATP) in the inhibitory non-adrenergic non-cholinergic (NANC) innervation of the rat gastric fundus. ATP (1-30 microM) produced biphasic responses consisting of concentration-dependent relaxations followed by concentration-dependent contractions. Suramin (200 microM) significantly reduced relaxations and abolished contractions to ATP. Under NANC conditions, electrical field stimulation (EFS) induced frequency-dependent relaxations. Suramin (200 microM) and the peptidase alpha-chymotrypsin (1 u ml(-1)) had the same effects on EFS-induced relaxations: their duration was reduced, but their magnitude was unaffected. Cumulative relaxations to vasoactive intestinal peptide (VIP; 0.1-100 nM), and to the VIP analogue pituitary adenylate cyclase activating peptide 1-27 (PACAP; 0.2-100 nM), were almost completely abolished by alpha-chymotrypsin (1 u ml(-1)), and were inhibited by suramin (3-200 microM) in an apparently competitive manner. Schild plot analysis indicated that suramin had pA(2) values of 5.1+/-0.2 (Hill slope=0.9+/-0.2) and 5.6+/-0.1 (Hill slope=1.0+/-0.1), against VIP and PACAP, respectively. Concentration-dependent relaxations to nitric oxide (1-30 microM) and cumulative relaxations to isoprenaline (0.1-300 nM) were not affected by suramin (200 microM). No conclusions can be made regarding the possible involvement of ATP in EFS-induced NANC relaxations. The results suggest that suramin acts as a competitive antagonist at VIP receptors in the rat gastric fundus.
Department of Anatomy and Cell Biology, University of Melbourne, Victoria 3010, Australia. KJenkinson@anatomy.unimelb.edu.au
K M
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Jenkinson
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004347:Drug Interactions; D005748:Gastric Fundus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D000318:Adrenergic beta-Agonists; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D018005:Receptors, Vasoactive Intestinal Peptide; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013498:Suramin; D000255:Adenosine Triphosphate; D007545:Isoproterenol