Selective down-regulation of adrenergic receptor subtypes in tissues from rats with pheochromocytoma

We have used an animal model of pheochromocytoma and radioligand-binding techniques to examine the effects of high levels of circulating norepinephrine and dopamine on adrenergic receptor subtypes in several peripheral tissues. New England Deaconess Hospital rats with transplanted pheochromocytomas were hypertensive and had levels of plasma norepinephrine and dopamine 50-fold greater than those of controls. The number of beta-adrenergic receptors in membranes prepared from the renal cortex and the left ventricle from these rats was decreased about 50%, but the animals had no significant decrease in the overall number of beta-adrenergic receptors in pulmonary membranes. beta-Receptor affinity was unaltered in animals with pheochromocytoma. Competition for [125I]iodocyanopindolol binding to beta-receptors by subtype-selective agents indicated a selective decrease of about 80% in the number of beta 1-adrenergic receptors in renal cortical and pulmonary membranes, without a decrease in beta 2-adrenergic receptor number. Rats with pheochromocytoma also had about a 70% decrease in the number of alpha 1-adrenergic receptors in membranes from renal cortex and lung, but no significant decrease in the number of alpha 1-adrenergic receptors in hepatic membranes and no decrease in the number of alpha 2-adrenergic receptors in renal cortical and hepatic membranes. These results indicate that rats in which pheochromocytomas are transplanted show adrenergic receptor subtype- and tissue-specific down-regulation. Although the selective down-regulation of alpha 1- and beta 1-adrenergic receptors may reflect a response to the preponderance of norepinephrine in these animals, the results indicate that different tissues and different adrenergic receptor subtypes may have varying susceptibility to down-regulation in response to increased circulating catecholamines in vivo.