An effect of ischemia on myocardial dihydropyridine binding sites.
The [3H]nitrendipine binding activity of sarcolemmal fragments isolated from aerobically perfused or ischemic rat hearts was studied. After 90 min aerobic perfusion, two populations of binding sites were detected--high affinity sites with KD of 0.24 +/- 0.04 nM and Bmax 313 +/- 110 fmol/mg protein, and low affinity sites with KD of 47.6 +/- 8.7 nM and Bmax 12.4 +/- 1.88 pmol/mg protein. Sixty minutes global ischemia significantly reduced the KD of the low (15.8 +/- 2.9 nM, P less than 0.03) but not of the high (0.22 +/- 0.05 nM) affinity sites. Under these same conditions the Bmax of both the high (82.4 +/- 14.5 fmol/mg protein, P less than 0.03) and low (6.1 +/- 1.7 pmol/mg protein, P less than 0.01) affinity binding sites was reduced but the sites retained their selectivity, with nifedipine displacing bound [3H]nitrendipine more potently than D600. Bay K 8644, when added upon reperfusion, promoted a dose-related increase in Ca2+ entry which was reduced by nifedipine, indicating that dihydropyridine binding sites can be activated after 60 min ischemia.
Nayler
W G
WG
Dillon
J S
JS
Elz
J S
JS
McKelvie
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000332:Aerobiosis; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D003327:Coronary Disease / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium