DIFFERENTIAL COUPLING OF GLUCAGON AND BETA-ADRENERGIC RECEPTORS WITH THE SMALL AND LARGE FORMS OF THE STIMULATORY G-PROTEIN

Glucagon receptors (GRs) and beta-adrenergic receptors (beta-ARs) stim ulate adenylate cyclase (AC) via G(s). The present study was performed to determine whether different cAMP-generating receptors share the sa me pool of G(s). In hepatocytes and liver plasma membranes from partia lly hepatectomized male rats, glucagon was more potent in stimulating AC than beta-adrenergic agonists, but the effects of glucagon and beta agonists on AC activity were not additive. This suggests that GRs and beta-ARs share the same pathway. Glucagon lowered the affinity of bet a agonists for beta-ARs in the presence of GTP gamma S, whereas beta a gonists had no effect on glucagon binding to GRs regardless of the pre sence or the absence of GTP gamma S. Therefore, the pool of G(s) coupl ed to GRs appears to include that coupled to beta-ARs. The alpha subun it of G(s) (G(s alpha)) exists in small (G(s alpha-S)) and large (G(s alpha-L)) forms. Recently, with a new method that uses tryptic digesti on, the G protein coupled to beta-ARs was identified as G(s-L) in part ially hepatectomized male rat livers because beta-adrenergic agonists promoted trypsinization of G(s alpha-L) but not of G(s alpha-S). By co ntrast, the present study showed that glucagon enhanced the sensitivit y of the two G(s alpha) isoforms to trypsin in a concentration-depende nt manner, indicating that GRs are coupled to both G(s alpha-S) and G( s alpha-L). In conclusion, GRs share a common G(s-L) with beta-ARs but are also coupled to another G(s), G(s-S), in partially hepatectomized male rat livers.