Subtype-selective down-regulation of rat renal cortical alpha- and beta-adrenergic receptors by catecholamines.
In the current studies, we have explored agonist-mediated down-regulation of adrenergic receptors in vivo. We infused catecholamines from sc implanted osmotic minipumps and examined the effects of the resultant increases in circulating levels of catecholamines on rat renal cortical alpha- and beta-adrenergic receptor subtypes, as assessed in radioligand binding studies. Infusion of epinephrine or norepinephrine (at 150 micrograms/kg X h) elevated plasma levels of each catecholamine 10- to 20-fold and decreased renal cortical alpha 1-receptor number about 50% without changing alpha 2-receptor number. Isoproterenol infusion (150 micrograms/kg X h) raised plasma levels of this catecholamine, but had no effect on the number of either alpha 1- or alpha 2-receptors. Renal cortical beta-adrenergic receptor number was decreased by infusion of all three catecholamines. However, the beta 1- and beta 2-adrenergic receptors were altered selectively by the different agonists. Infusion of norepinephrine decreased both beta 1- and beta 2-receptor number, but was more effective for the beta 1-receptors; this result was somewhat at variance with that we previously reported for rats bearing transplanted pheochromocytomas. The decrease in beta-receptor number due to epinephrine infusion was largely due to loss of the renal cortical beta 2-receptors. Infusion of isoproterenol decreased the number of both beta 1- and beta 2-receptors (69% and 75%, respectively). Infusion of norepinephrine maximally decreased the number of alpha 1-, beta 1-, and beta 2-receptors within 2 days, and the t 1/2 for receptor loss was about 12 h. beta-Receptors lost in response to isoproterenol infusion could not be recovered in a pellet prepared by high speed centrifugation of the supernatant derived from the preparation of renal cortical membranes. These results indicate that adrenergic receptor subtypes are differentially down-regulated by elevated levels of circulating catecholamines and that this differential loss of receptors depends on the nature of the receptor subtype, the agonist, and perhaps also whether catecholamines are infused rather than increased by pheochromocytoma.
D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine