Relationship between beta-adrenergic receptors and adenylate cyclase in HeLa cells
Henneberry, R.C.; Smith, C.C.; Tallman, J.F.
Nature 268(5617): 252-254
1977
ISSN/ISBN: 0028-0836 PMID: 196205 Document Number: 113666
The physiological actions of many hormones and neurotransmitters are mediated through activation of adenylate cyclase (Atp pyrophosphate lyase 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 entities4,5, probably the products of different genes6. We have found that He La 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 He La 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.