The metabolic effects of guanyl nucleotides on rat pancreatic acini permeabilized with streptolysin O suggest a widespread use of G proteins.
In streptolysin O permeabilized acini that were normally responsive to carbamylcholine and cholecystokinin octapeptide, amylase secretion was stimulated: a) by the stable guanyl nucleotides with a potency decreasing as follows: guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) greater than guanylyl-imidodiphosphate (GMP-PNP) = guanylyl-(beta, gamma-methylene)-diphosphonate (GMP-PCP), in the presence of 0.5 mM calcium and b) by calcium alone (EC50 3 microM). The maximal secretory effect of calcium alone (a 2-fold increase) was less effective than that of GTP gamma S and calcium offered in combination (an 8-fold increase). In the virtual absence of Ca2+, GTP gamma S still stimulated amylase release (a 3-fold increase) while 12-O-tetradecanoylphorbol 13-acetate (TPA) did not. The relative potencies of guanyl nucleotides were GTP gamma S greater than GMP-PNP = GMP-PCP = GTP on phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown, GTP gamma S greater than GMP-PNP greater than GMP-PCP = GTP on 45Ca2+ efflux, and GTP GMP-PNP = GMP-PCP = GTP gamma S on [1-14C]arachidonate efflux. Based on these data, the contribution of G proteins to stimulus-secretion coupling beyond the transduction of receptor signal is considered.
Winand
J
J
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Delporte
C
C
Poloczek
P
P
Cantraine
F
F
Dehaye
J P
JP
Christophe
J
J
D000681:Amylases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001426:Bacterial Proteins; D002118:Calcium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D013301:Streptolysins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001426:Bacterial Proteins; D007295:Inositol Phosphates; D013301:Streptolysins; C025964:streptolysin O; D016718:Arachidonic Acid; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C004805:5'-guanylylmethylenebisphosphonate; D006160:Guanosine Triphosphate; D000681:Amylases; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium