title: Effect of repeated administration of clenbuterol on the regulation of beta-adrenoceptors in the central nervous system of the rat.
abstract: The effect of the centrally acting beta-adrenoceptor agonist clenbuterol on beta-adrenergic responsiveness, beta-receptor density and N-protein coupling was studied in the rat cerebral cortex (which contains primarily beta 1-receptors) and cerebellum (containing mostly beta 2-receptors). The objective was to determine whether clenbuterol's effect on these variables was similar to that produced by standard antidepressants. When given to rats repeatedly, clenbuterol caused a decrease in beta-adrenergic responsiveness in slices from either the cerebral cortex or the cerebellum. The decreased beta-responsiveness in the cerebellum was associated with a decrease both in the density of beta-receptors and in receptor/N-protein coupling. In the cortex, only reduced receptor/N-protein coupling was observed by in vitro ligand-binding methods. However, when quantitative autoradiography was employed, clenbuterol treatment was found to reduce the binding of [125I]iodopindolol to beta 2-receptors throughout the brain, whereas binding to beta 1-receptors was not reduced. The down-regulation of beta 2-receptors by clenbuterol is due to its acting centrally as a beta 2-agonist. Although clenbuterol has about an equal affinity for beta 1-receptors and beta 2-receptors, no evidence was found for agonist activity of this drug at beta 1-receptors in the cerebral cortex. The strategies described here should be helpful in investigating important properties of centrally acting beta-agonists that might have potential as antidepressants.
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D002976:Clenbuterol / Q000008:administration & dosage*; D000242:Cyclic AMP / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage*; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C025716:ICI 89406; D000242:Cyclic AMP; D007545:Isoproterenol; D002976:Clenbuterol