Lack of beta adrenoceptor desensitization in brain following the dual noradrenaline and serotonin reuptake inhibitor venlafaxine.
Venlafaxine, a dual amine reuptake inhibitor, was utilized to delineate the role of the individual aminergic components of the 'serotonin/noradrenaline link' in modifying receptor-linked second messenger cascades. Venlafaxine (20 mg/kg i.p. bid for 10 days) failed to alter in normal animals either the density of beta adrenoceptors or the response of the beta adrenoceptor-coupled adenylate cyclase system to noradrenaline but significantly decreased the cyclic AMP response to noradrenaline in the brain of rats with selective depletion of brain serotonin by p-chlorophenylalanine. The studies provide evidence for a cross-talk between noradrenergic and serotonergic receptor cascades at the level of mechanisms involved in the desensitization of the beta adrenoceptor-coupled adenylate cyclase system.
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
I
I
Nalepa
D H
DH
Manier
D D
DD
Gillespie
S P
SP
Rossby
D E
DE
Schmidt
F
F
Sulser
D000262:Adenylyl Cyclases / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
D000262:Adenylyl Cyclases; D000242:Cyclic AMP; D003511:Cyclohexanols; D009638:Norepinephrine; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride