Effects of calcium channel inhibitors on the hypothermic response to oxotremorine in normo and hypercholinergic rats.
The Flinders Sensitive Line of rats (FSL) has been selectively bred to have increased sensitivity to cholinergic drugs. Typically, these rats react with twice as great a hypothermic effect to muscarinic agonists such as oxotremorine, as do similarly bred Flinders Resistant Line rats (FRL). We compared the effects of three chemically different calcium channel inhibitors (diltiazem, nicardipine and verapamil) on the hypothermia induced in FRL and FSL rats by oxotremorine (0.2 mg kg-1 s.c.). Each drug was injected i.p. in a dose of 20 mumol kg-1 30 min before oxotremorine. Methylatropine (2 mg kg-1 s.c.) was administered 15 min before oxotremorine to block the peripheral effects of the agonist. The hypothermic effect of oxotremorine in FSL rats was antagonized by nicardipine and diltiazem. In contrast, verapamil failed to influence the hypothermic response in FSL rats. Verapamil significantly (P less than 0.05) augmented oxotremorine hypothermia in FRL rats. Diltiazem and nicardipine were without effect on oxotremorine-induced hypothermia in FRL rats. There were no significant changes in temperature in separate groups of FRL and FSL rats treated with calcium channel inhibitors alone.
Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599.
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Pucilowski
D H
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Overstreet
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Rezvani
D S
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Janowsky
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D001286:Atropine Derivatives; D002121:Calcium Channel Blockers; D015259:Dopamine Agents; D004873:Ergolines; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D019257:Quinpirole; D010095:Oxotremorine; C006649:methylatropine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D001058:Apomorphine