[Noradrenaline-induced alterations in beta-adrenergic receptor-adenylate cyclase system of rat myocardium].
Although the agonist-induced down-regulation of beta-adrenergic receptors has been well documented, the investigations dealing with the agonist-induced changes in G-proteins are few and controversial. To elucidate the alterations in each components of the adenylate cyclase (AC) system, we infused subpressor doses of noradrenaline (NA) to WKY rats (20-week-old) for three different periods (3, - and 14 days) using osmotic minipumps. Beta-adrenergic receptor density measured by 125I-cyanopindolol binding assay, and forskolin-stimulated cyclase activity were both reduced markedly on the 3rd day of the treatment, and these effects persisted beyond the 14th day. Total amounts of the pertussis toxin substrates (inhibitory G-protein; Gi) increased significantly on the 7th day. On the other hand, those of the cholera toxin substrates (stimulatory G-protein: Gs) did not differ during the entire course of the treatment. We concluded that the down-regulations of the beta-adrenergic receptor and the catalytic protein were the adaptative response to the increased extracellular stimuli, and that the alterations observed in Gi might also have an important role to inhibit the transduction of excessive stimulatory signal.
Sato
K
K
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D002352:Carrier Proteins; D011943:Receptors, Adrenergic, beta; C020723:citrate-binding transport protein; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D009638:Norepinephrine