Sertraline, a selective inhibitor of serotonin uptake, induces subsensitivity of beta-adrenoceptor system of rat brain.
Subacute administration (b.i.d. for 4 days) of sertraline, a potent and selective inhibitor of serotonin uptake, was found to reduce cyclic AMP generation by the norepinephrine receptor-coupled adenylate cyclase in rat limbic forebrain slices and decrease the number of beta-adrenoceptors in rat cerebral cortex without affecting the affinity of [3H]dihydroalprenolol binding. Co-administration of sertraline and the serotonin agonist, quipazine, at doses at which neither agent had an effect, resulted in desensitization of norepinephrine receptor-coupled adenylate cyclase and down-regulation of beta-adrenoceptors. These findings suggest that increased serotonergic activity may be involved in the induction of subsensitivity of the beta-adrenoceptor system of rat brain by sertraline.
Koe
B K
BK
Department of Pharmacology, Pfizer Inc., Groton, CT 06340.
Koch
S W
SW
Lebel
L A
LA
Minor
K W
KW
Page
M G
MG
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D020280:Sertraline
D009281:Naphthalenes; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D012702:Serotonin Antagonists; D011814:Quipazine; D004082:Dihydroalprenolol; D015057:1-Naphthylamine; D000262:Adenylyl Cyclases; D020280:Sertraline