Hypothermia induced by cholinomimetic drugs is blocked by galanin: possible involvement of ATP-sensitive K+ channels.
Central administration of galanin in the mouse dose-dependently blocked the hypothermia induced by the muscarinic receptor agonist, 2-ethyl 8-methyl-2,8-diazospiro[4,5]decan-1,3-dion hydrobromide, RS86 (minimum effective dose, MED = 3 nmol) and the acetylcholinesterase inhibitor tetrahydroaminoacridine, (MED = 3 nmol). This inhibitory effect was reversed over the dose range (0.1, 0.3, 1, 3 nmol) by the galanin receptor antagonist galantide (MED = 0.3 nmol). Furthermore, the ATP-sensitive K+ channel blockers glibenclamide (MED = 1 nmol) and gliquidone (10 nmol) both prevented the inhibitory effects of galanin on RS86 induced hypothermia. Glibenclamide (10 nmol) also reversed the inhibitory effects of galanin on tetrahydroaminoacridine induced hypothermia. Preincubation of rat cortical membranes with galanin (10 nM, 1000 nM) in vitro had no effect on binding affinity, receptor number or pharmacology of the rat cortical muscarinic receptor. In contrast to the high affinity of glibenclamide, galanin only weakly displaced [3H]glibenclamide binding in mouse whole brain homogenates (36% at 10 microM). These studies suggest that the inhibitory effect of galanin on cholinergically mediated hypothermia induced by RS86 and tetrahydroaminoacridine may be exerted via an action at ATP-sensitive K+ channels but is unlikely to be acting directly at the site labelled by [3H]glibenclamide.
Patel
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Merck Sharpe and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK.
Hutson
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PH
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D019004:Galanin; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019832:N-Methylscopolamine; D009479:Neuropeptides / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013388:Succinimides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D013619:Tacrine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D007004:Hypoglycemic Agents; D009479:Neuropeptides; D010277:Parasympathomimetics; D010455:Peptides; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D013388:Succinimides; D013453:Sulfonylurea Compounds; C001886:2-ethyl-8-methyl-2,8-diazaspiro(4,5)decane-1,3-dione; D013619:Tacrine; D019004:Galanin; D000255:Adenosine Triphosphate; C010969:gliquidone; D005905:Glyburide; D019832:N-Methylscopolamine