title: Glucagon-(19-29) exerts a biphasic action on the liver plasma membrane Ca2+ pump which is mediated by G proteins.
abstract: We have recently shown that nanomolar concentrations of glucagon-(19-29), which can derive from native glucagon by proteolytic cleavage of the dibasic doublet Arg17-Arg18, inhibit the Ca2+ pump in liver plasma membrane vesicles independently of adenylyl cyclase activation (Mallat, A., Pavoine, C., Dufour, M., Lotersztajn, S., Bataille, D., and Pecker, F. (1987) Nature 325, 620-622). We report here that the regulation of the Ca2+ pump by glucagon-(19-29) is dependent on guanine nucleotides. In the presence of 10 microM guanosine 5'-3-O-(thio) triphosphate (GTP gamma S) or 75 microM GTP, glucagon-(19-29) caused a biphasic regulation of the Ca2+ pump. ATP-dependent Ca2+ transport was inhibited in the presence of 10 pM to 1 nM glucagon-(19-29), while higher concentrations of the peptide (1-100 nM) reversed the inhibition caused by lower ones. GTP gamma S alone, at high concentrations (100 microM), reproduced the inhibitory effect of glucagon-(19-29) and induced a 40% inhibition of the basal activity of the Ca2+ pump which was reversed by low concentrations of glucagon-(19-29) (10 pM to 1 nM). Treatment of rats with cholera toxin resulted in a 70% increase in the basal activity of the Ca2+ pump, a loss of sensitivity to GTP gamma S and to the biphasic regulation by glucagon-(19-29). Treatment with pertussis toxin did not affect the response of the Ca2+ pump to GTP gamma S and glucagon-(19-29). We conclude that glucagon-(19-29) can exert a biphasic effect on the Ca2+ pump which is mediated by G protein(s) sensitive to cholera toxin.
authors: Institut National de la Santé et de la Recherche Médicale, Unité 99, Hôpital Henri Mondor, Créteil, France.
authors: S
authors: S
authors: Lotersztajn
authors: C
authors: C
authors: Pavoine
authors: V
authors: V
authors: Brechler
authors: B
authors: B
authors: Roche
authors: M
authors: M
authors: Dufour
authors: D
authors: D
authors: Le-Nguyen
authors: D
authors: D
authors: Bataille
authors: F
authors: F
authors: Pecker
mesh_terms: D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D002772:Cholera Toxin / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D005934:Glucagon / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D010446:Peptide Fragments; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C039265:glucagon (19-29); D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D005934:Glucagon; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium