beta-Adrenergic receptor subtypes in the rat renal cortex. Selective regulation of beta 1-adrenergic receptors by pheochromocytoma.

Publisher Website
Google Scholar
Abstract
Radioligand binding techniques were used to characterize and to examine regulation of .beta.-adrenergic receptor subtypes on rat renal cortical membranes. Binding of the .beta.-adrenergic antagonist [125I] iodocyanopindolol was saturable with time and ligand concentration and demonstrated appropriate stereoselectivity and agonist rank order potency for binding to a .beta.-adrenergic receptor. From saturation binding isotherms, the KD and Bmax [maximum binding] values for [125I]iodocyanopindolol binding were 59 pM and 46 fmol/mg, respectively, and [125I]iodocyanopindolol appeared to bind to a single class of noncooperative sites. Computer analysis of competition by the subtype-selective antagonists practolol (.beta.1) and zinterol (.beta.2) for [125I]iodocyanopindolol binding indicated that the renal cortical .beta.-adrenergic receptors were 70% .beta.1 and 30% .beta.2. Treatment of the rats with 6-hydroxydopamine which decreased tissue norepinephrine levels 85% did not alter .beta.-receptor number or the relative percentage of the .beta.1 and .beta.2 subtypes. The regulation of renal .beta.-adrenergic receptor subtypes in vivo were examined using a new model system to produce elevated endogenous catecholamine levels. Pheochromocytomas were transplanted into normal rats, and these animals developed plasma norepinephrine levels 50-fold greater than controls. In renal membranes from rats bearing the tumor, .beta.-adrenergic receptor number was decreased 64%, from 54 .+-. 5 to 20 .+-. 4 fmol/mg, compared to controls. Computer analysis of practolol competition for [125I]iodocyanopindolol binding revealed that this decrease was due entirely to a loss of the .beta.1 receptor subtype. The .beta.1 receptor number decreased from 38 .+-. 7 to 8 .+-. 1 fmol/mg, while .beta.2 receptor number was not significantly altered. [125I]Iodocyanopindolol can be used to characterize renal cortical .beta.-adrenergic receptors. These receptors are primarily of the .beta.1 subtype. In the presence of elevated endogenous norepinephrine levels produced by pheochromocytoma, the .beta.1 receptor subtype is selectively down regulated.