Antagonism of adenosine 5'-triphosphate-induced relaxation by 2-2'-pyridylisatogen in the taenia of guinea-pig caecum.
1. 2-2' Pyridylisatogen tosylate (PIT) (greater than 2.5 muM) relaxed the guinea-pig isolated taenia caeci by an unknown mechanism. 2. With higher concentrations of PIT (greater than 12.5 muM) subsequent applications of adenosine 5'-triphosphate (ATP) (2-600 muM) revealed a blockade of the ATP receptors. The antagonism was characterized by a delayed onset of action (greater than 10 min incubation with 50 muM PIT) and eventually became irreversible (greater than 50 muM PIT for greater than 30 minutes). The antagonism was specific for ATP, was not competitive, and was not dependent upon the relaxant effect. 3. The presence of either acetylcholine (0.05-1.0 muM) or carbachol (0.05-1.0 muM) increased the antagonistic effect of PIT (50 muM) approximately five-fold. 4. Following prolonged exposure, PIT (50 muM for 90 min) did not block the inhibitory effects of fiedl stimulation (2 Hz, 10 s) of the taenia caeci in the presence of hyoscine (0.33 muM). These results do not support the purinergic nerve hypothesis.
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002432:Cecum / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007510:Isatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011955:Receptors, Drug; D013268:Stimulation, Chemical; D013997:Time Factors
D007211:Indoles; D011725:Pyridines; D011955:Receptors, Drug; D007510:Isatin; D000255:Adenosine Triphosphate