Ten day administration of desipramine produces an increase in KL/KH for beta-receptors in rat hippocampus.
The action of chronic desipramine administration on agonist and antagonist binding to beta-adrenoceptors was investigated in rat frontal cortex and hippocampus. Ten day treatment with desipramine (10 mg/kg per day i.p.) resulted in a significant 34% decrease in the density of beta-adrenoceptors in membranes from rat frontal cortex but not hippocampus. The KD values for antagonist (iodocyanopindolol) did not change in either tissue after the desipramine treatment. Desipramine had no effect on the affinity of the agonist isoproterenol in frontal cortex. The percentage of receptors in the high affinity state for isoproterenol (% RH) decreased by 11% in the membranes from frontal cortex after desipramine administration. In contrast, in hippocampal membranes, desipramine treatment produced a decrease in KH (dissociation constant for isoproterenol binding to the high affinity state) and consequently a 137% increase in the ratio of dissociation constants for isoproterenol to the low and high affinity conformations (KL/KH; an putative index of coupling). This observation is new and suggests possible supercoupling of beta-adrenoceptors in hippocampus during desipramine treatment. Thus, in addition to desensitization of beta-adrenoceptors in rat frontal cortex ten day administration of desipramine causes a change compatible with supercoupling of beta-receptors in hippocampal membranes.
Turkka
J
J
Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Gurguis
G
G
Potter
W Z
WZ
Linnoila
M
M
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007545:Isoproterenol / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D003891:Desipramine