Antagonism by nifedipine of contraction and Ca2+ ‐influx evoked by ATP in guinea‐pig urinary bladder

Abstract

1 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. 2 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. 3 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). 4 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 antagonized by nifedipine. 5 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.