Antagonism by nifedipine of contraction and Ca2(+)-influx evoked by ATP in guinea-pig urinary bladder.
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, omega-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 microM) was fully reversed by administration of Bay K 8644 (0.1 microM). 4. ATP (100 microM) 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 evoked by the nucleotide were completely antagonized by nifedipine. 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.
Katsuragi
T
T
Department of Pharmacology, Fukuoka University, School of Medicine, Japan.
Usune
S
S
Furukawa
T
T
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005453:Fluorescence; D016257:Fura-2; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D001572:Benzofurans; D002121:Calcium Channel Blockers; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2