The alpha2-adrenergic receptor is more effective than the galanin receptor in activating G-proteins in RINm5F beta-cell membranes.
Activated receptors for galanin and norepinephrine, and for several other agonists, inhibit insulin release from pancreatic beta-cells via pertussis toxin-sensitive Gi- and Go-proteins and by acting on at least four cellular mechanisms. These mechanisms include repolarization via activation of the ATP-sensitive potassium (K ATP) channel, inhibition of adenylyl cyclase, and inhibition by unknown mechanism at a "distal" site. For norepinephrine and galanin there is also inhibition of the L-type Ca2+ channel. Consequently, during simultaneous activation by multiple agonists, the effectiveness with which a receptor interacts with the G-proteins will, to some extent, determine the responses. This could have important consequences for the beta-cell. Therefore, the G-protein interactions of two activated receptors, those for norepinephrine and galanin, were compared in the same beta-cell membranes. Measurements were made of the rates of receptor-G-protein interaction (by GTPgammaS binding) and of the rates of turnover of G-proteins (by GTPase activity). A comparison was also made of the ability of norepinephrine and galanin to facilitate ADP ribosylation of the alpha-subunits of Gi and Go by cholera toxin (CTX). Such CTX-induced ADP ribosylation of Gi and Go occurs during G-protein interaction with an activated receptor. By measurement of the number of receptors in the membrane preparation used, the relative effectiveness of the two receptors was assessed. The alpha2-adrenergic receptor was found to be markedly more effective than the galanin receptor in activating G-proteins.
Gillison
S L
SL
Department of Pharmacology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Straub
S G
SG
Sharp
G W
GW
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002772:Cholera Toxin / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D019004:Galanin / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D007515:Islets of Langerhans; D007700:Kinetics; D009243:NAD / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000502:physiology*
D018341:Receptors, Adrenergic, alpha-2; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019004:Galanin; D002772:Cholera Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D003000:Clonidine; D009638:Norepinephrine