P(2) purinoceptors account for the non-nitrergic NANC relaxation in the rat ileum.
The transmitters involved in the non-nitrergic component of the non-adrenergic, non-cholinergic (NANC) inhibitory response of the rat small intestinal longitudinal muscle to electrical field stimulation of its nerves is a matter of controversy. The present study is the first one to utilise a combination of a nitric oxide synthase inhibitor and a P(2) purinoceptor antagonist for studying this response. We found that the P(2) purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 5x10(-5) M) abolished the non-nitrergic NANC relaxation to electrical field stimulation (10 Hz). PPADS alone provided a significant, moderate inhibitory action. PPADS specifically inhibited relaxations due to exogenous adenosine 5'-triphosphate (ATP) or alpha,beta-methylene ATP. The guanylate cyclase blocker 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10(-6) M) did not add to the inhibitory action of N(G)-nitro-L-arginine on field stimulation-induced relaxation. ODQ abolished the relaxant effect of the nitric oxide donors nitroglycerin or sodium nitroprusside. These data indicate that: (1) nitric oxide and ATP fully account for the field stimulation-induced relaxation in the rat ileal strip under the experimental conditions of this study, and (2) no ODQ-sensitive guanylate cyclase-mediated mechanism is involved in the non-nitrergic component of the NANC relaxation.
Benkó
Rita
R
Department of Pharmacology and Pharmacotherapy, Division of Pharmacodynamics, University Medical School of Pécs, Szigeti u. 12, H-7643, Pécs, Hungary.
Undi
Sarolta
S
Wolf
Matyas
M
Magyar
Klara
K
Tóvölgyi
Zsuzsanna
Z
Rumbus
Zoltan
Z
Barthó
Lorand
L
D000818:Animals; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D058919:Purinergic P2 Receptor Antagonists; D011810:Quinoxalines; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D009599:Nitroprusside; D019335:Nitroarginine; D013779:Tetrodotoxin; D011732:Pyridoxal Phosphate; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D005996:Nitroglycerin