Identification of calcium-channel receptors in intact animals.
In this study, we demonstrate the in vivo labeling by [3H]nitrendipine ([3H]NTD) of peripheral tissues and the brain in Sprague-Dawley rats. Specific binding is decreased in a dose-dependent manner by nifedipine, with a mean inhibitory dose of 2-10 mg/kg (i.p.). Thin-layer chromatography of the particulate-bound radioactivity reveals that the predominant tritiated drug bound in the left ventricle and the cerebral cortex is [3H]NTD, whereas metabolites constitute the main species in the liver. Peak radioactivity is seen at 15 min following an intravenous injection of [3H]NTD. Highly perfused tissues such as the heart, brain, and lung have significant [3H]NTD binding. In contrast to previously reported in vitro studies, [3H]NTD binding is low in the aorta, skeletal muscle, and ileum. This in vivo animal model is suitable for pharmacokinetic and physiological studies of the calcium channel in intact animals.
Roeske
W R
WR
Lee
H R
HR
Yamamura
H I
HI
Schoemaker
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels; D002540:Cerebral Cortex / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007082:Ileum / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009568:Nitrendipine; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium