Properties of beta-adrenergic receptors of cultured mammalian cells. Interaction of receptors with a guanine nucleotide-binding protein in membranes prepared from L6 myoblasts and from wild-type and cyc- S49 lymphoma cells.

Abstract

The radiolabeled agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) and antagonist [125I]iodopindolol ([125I]IPIN) were used to investigate the properties of beta-adrenergic receptors on membranes prepared from L6 myoblasts and S49 lymphoma cells. The high affinity binding of (-)-[3H]HBI to membranes prepared from L6 myoblasts was stereoselectively inhibited by the active isomers of isoproterenol and propranolol. The density of receptors determined with (-)-[3H]HBI was less than that determined with [125I]IPIN. The binding of (-)-[3H]HBI was inhibited by guanine nucleotides, suggesting an agonist-mediated association of the receptor with a guanine nucleotide-binding protein, presumably the stimulatory guanine nucleotide-binding protein (Ns) of adenylate cyclase. Results obtained in studies with membranes prepared from wild-type S49 lymphoma cells and the adenylate cyclase-deficient variant (cyc-) were similar to those obtained in experiments carried out with membranes prepared from L6 myoblasts. Thus, the high affinity binding of (-)-[3H]HBI to membranes prepared from wild-type and cyc- S49 lymphoma cells was stereoselectively inhibited by the active isomers of isoproterenol and propranolol, and was inhibited by GTP. Moreover, the density of sites determined with (-)-[3H]HBI was less than that determined with [125I]IPIN. These results suggest either that cyc- cells contain a partially functional Ns, or alternatively, that the inhibitory guanine nucleotide-binding protein (Ni) is capable of interacting with beta-adrenergic receptors.

• Authors: S N Abramson, P B Molinoff
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 260 Issue 27 Pg. 14580-8 (Nov 25 1985) ISSN: 0021-9258 [Print] United States
• PMID: 2997214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Adrenergic, beta
• Propranolol
• GTP-Binding Proteins
• Adenylyl Cyclases
• Isoproterenol

Topics

• Adenylyl Cyclases (metabolism)
• Animals
• Cell Line
• Cell Membrane (metabolism)
• GTP-Binding Proteins (metabolism)
• Isoproterenol (pharmacology)
• Kinetics
• Lymphoma (metabolism)
• Mice
• Muscles (metabolism)
• Propranolol (pharmacology)
• Receptors, Adrenergic, beta (drug effects, metabolism)