title: Clenbuterol increases norepinephrine release from rat brain slices by a calcium- and receptor-independent mechanism.
abstract: Clenbuterol (10-100 microM), a beta 2-adrenergic agonist, potentiated basal (unstimulated) and electrical stimulation-evoked release of 3H-norepinephrine from cerebral cortical slices in a concentration-dependent manner. The beta-adrenergic antagonists propranolol and ICI 118,551 did not antagonize the facilitatory effect of clenbuterol on basal 3H-norepinephrine efflux. Selective down-regulation of beta 2-adrenergic receptors produced by chronic administration of clenbuterol also did not alter this effect of in vitro clenbuterol, despite marked reductions in the density of these receptors. These results suggest that the increase in basal efflux of 3H-norepinephrine observed with clenbuterol was not mediated by beta 2-adrenergic receptors. The facilitatory effect of clenbuterol on basal 3H-norepinephrine efflux was Ca(2+)-independent, which may indicate an amphetamine-like mechanism of action. The enhanced basal efflux of 3H-norepinephrine produced by clenbuterol was stereoselective; there was a four-fold increase in basal 3H-norepinephrine efflux with the (+)-isomer of clenbuterol compared with that induced by the (-)-isomer; this contrasts with the stereoselectivity of the isomers for interacting with beta 2-adrenergic receptors. The present results may explain some of the behavioral actions of clenbuterol, particularly those observed after long-term treatment, and may be relevant to the antidepressant actions of this compound.
authors.affiliation: Department of Pharmacology and Therapeutics, Louisiana State University Medical School, Shreveport 71130.
authors.forename: K D
authors.initials: KD
authors.lastname: Murugaiah
authors.forename: J M
authors.initials: JM
authors.lastname: O'Donnell
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002976:Clenbuterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004558:Electric Stimulation; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D002118:Calcium; D009638:Norepinephrine; D002976:Clenbuterol