Binding characteristics of the calcium channel antagonist [3H]-nitrendipine in tissues from ethanol-dependent rats.
Male Sprague-Dawley rats were made physically dependent on ethanol by exposure to ethanol vapour in inhalation chambers for 6-10 days. Animals were sacrificed immediately after removal from the chambers. After sacrifice, membrane preparations from cerebral cortex, heart, vas deferens and thigh skeletal muscle were prepared and studied to determine the characteristics of [3H]-nitrendipine binding. In membranes from cerebral cortex, the number of binding sites (Bmax) was increased 40% in preparations from ethanol-dependent rats compared to controls. Similar results were obtained in heart (Bmax increased 125%), vas deferens (Bmax increased 50%) and skeletal muscle (Bmax increased 33%). Binding affinity (Kd) in all these tissues was unchanged. Membranes from cortex and heart were studied more extensively. Displacement studies using other dihydropyridines and the effects of ionic composition on [3H]-nitrendipine binding provided no evidence to suppose that the binding sites induced by the development of ethanol dependence were from a population different from those in control tissues. The results suggest a generalised 'up-regulation' of the dihydropyridine-sensitive subclass of voltage operated calcium channels in excitable tissues from ethanol-dependent rats.
Guppy
L J
LJ
Department of Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada.
Littleton
J M
JM
D000437:Alcoholism / Q000473:pathology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002540:Cerebral Cortex / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009568:Nitrendipine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015854:Up-Regulation / Q000502:physiology; D014649:Vas Deferens / Q000473:pathology
D015220:Calcium Channels; D009568:Nitrendipine