Adrenergic receptors in human and experimental pheochromocytoma

Radioligand binding to adrenergic receptors has become an important technique for identification and quantitation of these receptors. In this article we review our recent findings using subtype-selective radioligands for studying alpha 1 (e.g., [3H]prazosin) and alpha 2 (e.g. [3H]yohimbine) receptors in human platelets and rat renal cortical membranes, and we report new results on changes in adrenergic receptors of patients and animals with pheochromocytoma. Five patients with pheochromocytoma were tested prior to surgery. The number of alpha 2-adrenergic receptors on platelets from these patients and the affinity of these receptors for [3H]yohimbine were similar to values for control subjects. In rats with a transplantable pheochromocytoma we found a 50-fold increase in plasma norepinephrine levels. The number of renal cortical beta-adrenergic receptors (identified using [125I]iodohydroxybenzylpindolol) and alpha 1-adrenergic receptors were decreased while the number of alpha 2-adrenergic receptors did not change. Receptor affinities for radioligands were unaltered in animals with pheochromocytoma. These findings indicate that pheochromocytoma is associated with selective decreases in the number of renal beta- and alpha 1-adrenergic receptors without changing alpha 2-adrenergic receptor number or affinity. Furthermore, the number and affinity of alpha 2-adrenergic receptors are not altered in platelets of patients with pheochromocytoma. We conclude that down regulation (an agonist-mediated decrease in receptor number) occurs in vivo for some, but not all, types of adrenergic receptors.