Evidence for the stabilisation of the high-affinity state of beta-adrenoceptors by an endogenous factor in rat brain.
Inhibition of binding of the labelled antagonist (-)[3H]CGP 12177 by the full agonist (-)isoproterenol results in shallow competition curves, characteristic of the presence of both high- and low-affinity states of beta-adrenoceptors (betaAR). When in excess, the GTP analog 5'-guanylylimidodiphosphate (GppNHp) is expected to convert all receptors in the high-affinity state to the low-affinity state. However, in the rat cortex and cerebellum synaptosomes, a proportion of the betaAR in the high-affinity state was GppNHp-insensitive. This apparent GppNHp-insensitivity decreased with decreasing temperature of incubation. Moreover, it was totally abolished by the gentle treatment of membranes with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). We propose that a protein factor interacts with the betaAR/Gs protein complex and that it induces the GppNHp-insensitivity. This factor would be released by CHAPS in a functional form because it may regenerate the GppNHp-insensitivity after concentration and reconstitution with CHAPS-treated membranes. It is likely that the factor acts as a stabiliser of betaAR in the high-affinity state.
Garnier
V
V
Département de Pharmacologie, Faculté de Médecine de Paris, 8 rue du Général Sarrail, Cretéil, F-94010, France.
Zini
R
R
Morin
D
D
Tillement
J P
JP
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002793:Cholic Acids / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000378:metabolism; D008297:Male; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D013696:Temperature
D002793:Cholic Acids; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D019204:GTP-Binding Proteins; D007545:Isoproterenol; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate; C033394:CGP 12177