ANTAGONISM BY NIFEDIPINE OF CONTRACTION AND CA2+-INFLUX EVOKED BY ATP IN GUINEA-PIG URINARY-BLADDER

The effects of Ca2+-antagonists, especially nifedipine, on contraction and increase of intracellular Ca2+ (Fura-2/AM method) evoked by ATP were evaluated in a thin outer layer segment of guinea-pig urinary bladder. The ATP-evoked contraction was markedly inhibited by dihydropyridine-type Ca2+ antagonists, such as nifedipine and nitrendipine, but not by D-600, ω-conotoxin and tetramethrin. This antagonism by nifedipine of ATP-evoked contractions was competitive from the Schild plot analysis, the pA2 value being 8.23. The reduction of ATP-evoked contraction by nifedipine (0.1 μM) was fully reversed by administration of Bay K 8644 (0.1 μM). ATP (100 μM) caused an increase of fluorescence brightness after loading Fura-2/AM, which was coupled with a contraction of the bladder. Both the contraction and the elevation of intracellular Ca2+ evoked by the nucleotide were completely onized by nifedipine. These results suggest that ATP may activate the dihydropyridine-sensitive, voltage-dependent Ca2+-channels in a direct or indirect fashion and, thereby, elicit a contraction of the bladder.