@article{oai:sapmed.repo.nii.ac.jp:00014802, author = {土屋, 文明 and 齋藤, 利和}, issue = {1}, journal = {札幌医学雑誌 = The Sapporo medical journal, The Sapporo medical journal}, month = {Feb}, note = {The effects of desipramine (DMI) treatment on a rat cortical beta-adrenergic receptor- coupled adenylate cyclase (AC) system were investigated. Continuous treatment (1-3 days) of rats with desipramine (10 mg/kg, twice per day) caused a decrease in guanyl-5' -yl-imidodiphosphate [Gpp(NH)p]- stimulated AC activity in the cerebral cortical membrane. The decrease in the [Gpp(NH)p] - stimulated AC activity was more rapid and greater than the decrease in the number of beta-receptors in the cerebral cortical membrane of desipramine treated rats, indicating that the decrease in the enzyme activity, occurring at an early stage of the treatment, was not accounted for solely by the decrease in the receptor number. Although AC activity in the presence of a saturated level of Gpp(NH)p (Vmax) was not altered, the concentration of Gpp(NH)p required for the half-maximal activation of AC (EC?? for activation) was shifted from 0.73μM to 1.62μM in the membrane of 3 day-DMI treated rats. However, the concentration of Gpp(NH)p required for the half maximal inhibition of forskolin-stimulated AC (EC?? for inhibition) was not altered by 3 day-DMI treatment. The time course of activation of cortical AC activity by Gpp(NH)p was altered and the T1/2 for activation increased from 1.3 minutes to 2.0 minutes by the 3 day-DMI treatment. Three day-DMI treatment caused a decrease in the EC?? value for isoproterenol activation of AC from 30.7 nM to 22.9 nM in the rat cortical membrane. These results suggest that DMI decreases the affinity of Gs-protein to guanine nucleotides and consequently inhibits the high-affinity state breakdown process of beta-adrenergic receptor in the receptor-AC coupling system of the rat cerebral cortex. However, DMI has no or little effect on Gi protein.}, pages = {15--24}, title = {三環系抗うつ薬desipramineのラット大脳皮質β-adrenaline受容体adenylatecyclase共役機構への影響}, volume = {58}, year = {1989} }