ANTAGONISM OF ADENOSINE 5′‐TRIPHOSPHATE‐INDUCED RELAXATION BY 2‐2′‐PYRIDYLISATOGEN IN THE TAENIA OF GUINEA‐PIG CAECUM

Abstract

1 2-2′Pyridylisatogen tosylate (PIT) (>2.5 μM) relaxed the guinea-pig isolated taenia caeci by an unknown mechanism. 2 With higher concentrations of PIT (>12.5 μM) subsequent applications of adenosine 5′-triphosphate (ATP) (2-600 μM) revealed a blockade of the ATP receptors. The antagonism was characterized by a delayed onset of action (>10 min incubation with 50 μM PIT) and eventually became irreversible (>50 μM PIT for >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 μM) or carbachol (0.05-1.0 μM) increased the antagonistic effect of PIT (50 μM) approximately five-fold. 4 Following prolonged exposure, PIT (50 μM for 90 min) did not block the inhibitory effects of field stimulation (2 Hz, 10 s) of the taenia caeci in the presence of hyoscine (0.33 μM). These results do not support the purinergic nerve hypothesis.