Subtype-Selective Down-Regulation of Rat Renal Corticalα-andβ-Adrenergic Receptors by Catecholamines*

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Abstract
In the current studies, we have explored agonistmediated 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 α- and β-adrenergic receptor subtypes, as assessed in radioligand binding studies. Infusion of epinephrine or norepinephrine (at 150 μg/kg-h) elevated plasma levels of each catecholamine 10- to 20-fold and decreased renal cortical α1-receptor number about 50% without changing α2-receptor number. Isoproterenol infusion (150 ng/ kg-h) raised plasma levels of this catecholamine, but had no effect on the number of either α1- or α2-receptors. Renal cortical β-adrenergic receptor number was decreased by infusion of all three catecholamines. However, the ft- and β2-adrenergic receptors were altered selectively by the different agonists. Infusion of norepinephrine decreased both β1- and β2-receptor number, but was more effective for the ft-receptors; this result was somewhat at variance with that we previously reported for rats bearing transplanted pheochromocytomas. The decrease in β- receptor number due to epinephrine infusion was largely due to loss of the renal cortical β2-receptors. Infusion of isoproterenol decreased the number of both ft- and β2-receptors (69% and 75%, respectively). Infusion of norepinephrine maximally decreased the number of α1-, β1-, and β2-receptors within 2 days, and the t½ for receptor loss was about 12 h. β-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. (Endocrinology117: 2182–2189, 1985)