Characterization of calcium channel antagonist binding sites labeled by [3H]nitrendipine in porcine coronary artery and aorta.
The receptor sites for dihydropyridine calcium channel antagonists in porcine coronary artery were characterized with [3H]nitrendipine (NTD), and were compared with those in the thoracic aorta. Specific [3H]NTD binding in the coronary artery and aorta was saturable, reversible and of high affinity. These sites showed a pharmacological specificity and stereoselectivity characteristic of the receptor sites for dihydropyridine calcium channel antagonists. The pharmacological potencies of nitrendipine, nifedipine, nisoldipine, (+)-PN 200-110 and (-)-PN 200-110 in the isolated porcine coronary artery correlated well with their potencies in competing for [3H]NTD binding sites. The Hill coefficients for the competition curves for these antagonists in the porcine coronary artery and aorta were close to one. Verapamil partially inhibited specific [3H]NTD binding in both tissues. The [3H]NTD binding was increased by Mg2+ and Ca2+ but was markedly reduced by EDTA. Thus, the present study has shown that [3H]NTD selectively labels the pharmacologically relevant dihydropyridine receptors in the porcine coronary artery and that there is no significant difference between the binding characteristics of the receptor sites in the coronary artery and aorta of pigs.
Yamada
S
S
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Harada
Y
Y
Nakayama
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009568:Nitrendipine; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium