Relationship between β-adrenergic receptors and adenylate cyclase in HeLa cells

Abstract

THE physiological actions of many hormones and neurotransmitters are mediated through activation of adenylate cyclase (ATP pyrophosphate lyase [cyclising] EC 4.6.1.1) by specific cell surface receptors for each substance. The consequent increases in intracellular cyclic AMP lead to activation of protein kinases and a host of alterations in cell physiology, depending on the type of cell stimulated¹. Adrenergic receptors, responsive to β-hydroxylated catecholamines, were divided into α- and β-types by Ahlquist² using classical pharmacological techniques. The β-adrenergic effects of catecholamines occur through a receptor-mediated stimulation of adenylate cyclase activity³. Although β-adrenergic receptors have often been described as ‘tightly coupled’ to adenylate cyclase, recent evidence suggests that the receptor and the enzyme are physically discrete entities^4,5, probably the products of different genes⁶. We have found that HeLa cells contain β-adrenergic receptors and that the number of receptors per cell, but not the cellular content of adenylate cyclase, increases markedly during exposure of the cell to butyrate⁷. Here we present direct evidence that the HeLa cell β-adrenergic receptor can exist in a form either ‘coupled’ to or ‘uncoupled’ from adenylate cyclase. A model system for studies of receptor–adenylate cyclase interactions is described, and preliminary results of studies on the mechanism of coupling are reported.