The serotonin/norepinephrine-link in brain. II. Role of serotonin in the regulation of beta adrenoceptors in the low agonist affinity conformation.
The present studies were undertaken to characterize further the role of serotonin (5-HT) in the regulation of the norepinephrine (NE) beta adrenoceptor coupled adenylate cyclase system in the rat cortex. Although 5-HT in vitro did not influence maximum binding and Kd values of [3H]dihydroalprenolol binding or the IC50 value for isoproterenol as estimated from competition binding curves in cortical tissue from control animals, 5-HT abolished the increase in beta adrenoceptor number and the marked elevation of the IC50 value for isoproterenol in cortical membrane preparations after selective lesions with 5,7-dihydroxytryptamine (5,7-DHT). Nonlinear regression analysis of competition binding curves revealed that the increase in the maximum binding of beta adrenoceptors after 5,7-DHT is due exclusively to an increase in beta adrenoceptors in the agonist low affinity conformation and that it is this receptor population that is reduced by nanomolar concentrations of 5-HT. The increase in the density of beta adrenoceptors in the low affinity conformation occurred approximately 11 days after the lesions and remained elevated throughout the experimental period of 28 days. Ritanserin in a dose that virtually abolished 5-HT2 receptor binding in cortex did not mimic the effect of 5,7-DHT.(ABSTRACT TRUNCATED AT 250 WORDS)
Gillespie
D D
DD
Department of Pharmacology, Vanderbilt University School of Medicine, Tennessee.
Manier
D H
DH
Sanders-Bush
E
E
Sulser
F
F
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D007650:Ketanserin; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine