Abstract
A comparison was made of the effects of cholera toxin and p[NH]ppG on the binding affinity of beta-adrenergic receptors in toad erythrocyte membranes. This was determined by studying the ability of isoproterenol and propranolol to compete for the receptor with (-)-[3H]dihydroalprenolol. p[NH]ppG decreased the receptor affinity for the agonist isoproterenol (i.e. a 'right' shift in the displacement-concentration curve), but was without effect on the affinity for the antagonist propranolol. Toad erythrocyte membranes after treatment with cholera toxin exhibited increased receptor affinity for isoproterenol (i.e. a 'left' shift in the displacement curve), but did not affect the affinity for propranolol. p[NH[ppG was able to exert its right shift even in cholera-toxin treated membranes. The ability of cholera toxin to alter beta-adrenergic-receptor affinity is interpreted as further evidence that the toxin affects the nucleotide-regulatory component of adenylate cyclase. The regulatory component affected may be the catecholamine-sensitive guanosine triphosphatase.
MeSH Terms
Alprenolol/metabolism
Animals
Anura
Cholera Toxin/pharmacology
Erythrocyte Membrane/metabolism
Erythrocytes/metabolism
Guanosine Triphosphate/analogs & derivatives
Guanylyl Imidodiphosphate/pharmacology
Isoproterenol/metabolism
Propranolol/metabolism
Receptors, Adrenergic/drug effects
Receptors, Adrenergic, beta/drug effects,metabolism
Chemicals
Receptors, Adrenergic
Receptors, Adrenergic, beta
Guanylyl Imidodiphosphate
Guanosine Triphosphate
Alprenolol
Cholera Toxin
Propranolol
Isoproterenol
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Fischer J
Sharp G W
References (26)
26 references, click to expand
-
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75
PMID: 14907713
-
Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site.
Proc Natl Acad Sci U S A. 1977 Aug;74(8):3307-11
PMID: 198781
-
Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes.
Biochim Biophys Acta. 1976 Dec 8;452(2):538-51
PMID: 188466
-
Altered guanine nucleotide hydrolysis as basis for increased adenylate cyclase activity after cholera toxin treatment.
J Biol Chem. 1977 Jun 10;252(11):3766-74
PMID: 863902
-
The activation of adenylate cyclase by cholera toxin: possible interaction with the nucleotide regulatory site.
Ciba Found Symp. 1976;(42):89-108
PMID: 186240
-
Cholera toxin requires oxidized nicotinamide-adenine dinucleotide to activate adenylate cyclase in purified rat liver plasma membranes.
Biochem J. 1977 Mar 1;161(3):639-42
PMID: 192202
-
Hydrolysis of nicotinamide adenine dinucleotide by choleragen and its A protomer: possible role in the activation of adenylate cyclase.
Proc Natl Acad Sci U S A. 1976 Dec;73(12):4424-7
PMID: 188038
-
Effect of gangliosides and substrate analogues on the hydrolysis of nicotinamide adenine dinucleotide by choleragen.
Proc Natl Acad Sci U S A. 1977 Jan;74(1):74-8
PMID: 13371
-
Mechanism of action of choleragen. Evidence for ADP-ribosyltransferase activity with arginine as an acceptor.
J Biol Chem. 1977 Apr 10;252(7):2455-7
PMID: 139409
-
Mode of action of cholera toxin: stabilization of catecholamine-sensitive adenylate cyclase in turkey erythrocytes.
Proc Natl Acad Sci U S A. 1974 Aug;71(8):3299-303
PMID: 4370199
-
Toxins of Vibrio cholerae and Escherichia coli stimulate adenyl cyclase in rat fat cells.
Nature. 1974 May 24;249(455):371-3
PMID: 4366779
-
Studies on the mode of action of cholera toxin. Effects on solubilized adenylate cyclase.
J Clin Invest. 1974 Apr;53(4):1202-5
PMID: 4815085
-
Stimulation of intestinal adenyl cyclase by cholera toxin.
Nature. 1971 Jan 22;229(5282):266-9
PMID: 4323551
-
Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins.
J Clin Invest. 1971 Jun;50(6):1218-30
PMID: 4325309
-
Holocatalytic state of adenylate cyclase in turkey erythrocyte membranes: formation with guanylylimidodiphosphate plus isoproterenol without effect on affinity of beta-receptor.
J Cyclic Nucleotide Res. 1976;2(1):47-56
PMID: 818136
-
Activation of adenylate cyclase by cholera toxin in rat liver homogenates.
J Clin Invest. 1976 Feb;57(2):450-8
PMID: 176181
-
Beta-Adrenergic receptor interactions. Direct comparison of receptor interaction and biological activity.
J Biol Chem. 1976 Mar 10;251(5):1239-46
PMID: 1254566
-
Regulation of adenylate cyclase coupled beta-adrenergic receptors.
Recent Prog Horm Res. 1976;32:597-632
PMID: 785560
-
Regulation of beta-adrenergic receptors by guanyl-5'-yl imidodiphosphate and other purine nucleotides.
J Biol Chem. 1976 Aug 10;251(15):4686-92
PMID: 947904
-
Effects of cholera toxin on adenylate cyclase. Studies with guanylylimidodiphosphate.
J Clin Invest. 1975 Nov;56(5):1345-9
PMID: 1184756
-
Activation of pigeon erythrocyte membrane adenylate cyclase by guanylnucleotide analogues and separation of a nucleotide binding protein.
J Biol Chem. 1975 Feb 10;250(3):867-76
PMID: 1120776
-
Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro.
Proc Natl Acad Sci U S A. 1975 Jun;72(6):2064-8
PMID: 166378
-
Identification of adenylate cyclase-coupled beta-adrenergic receptors in frog erythrocytes with (minus)-[3-H] alprenolol.
J Biol Chem. 1975 Jul 10;250(13):4869-76
PMID: 238972
-
Solubilization and characterization of the beta-adrenergic receptor binding sites of frog erythrocytes.
J Biol Chem. 1976 Apr 25;251(8):2374-84
PMID: 4447
-
An agonist-specific effect of guanine nucleotides on binding to the beta adrenergic receptor.
Mol Pharmacol. 1976 Mar;12(2):335-9
PMID: 4726
-
Differentiation of receptor systems activated by sympathomimetic amines.
Nature. 1967 May 6;214(5088):597-8
PMID: 6036174