Comparative effects of GLP-1-(7-36) amide, oxyntomodulin and glucagon on rabbit gastric parietal cell function.
We have investigated in vitro, the effects of glucagon-like peptide-1-(7-36) amide (GLP-1-(7-36) amide), oxyntomodulin and glucagon on two rabbit parietal cell-enriched fractions (F3, F3n), with parietal cell contents of 60% and 88%, respectively. Histamine (10(-5) M) stimulated [14C]aminopyrine accumulation to an amount of 850% in excess of the basal level, whereas GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-6) M) induced increases of 50% and 30%, respectively. With a histamine concentration of 10(-6) M, [14C]aminopyrine accumulation was stimulated to 498% in excess of the basal level; GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-7) M) induced increases of 18% and 15%, respectively. With these parameters, oxyntomodulin[19-37] and glucagon were without effect. Specific binding of [125I]GLP-1-(7-36) amide to parietal cell plasma membranes was inhibited dose-dependently by GLP-1-(7-36) amide, oxyntomodulin and glucagon with inhibitory concentrations of 0.25 nM, 65 nM and 800 nM, respectively. No specific binding of [125I]oxyntomodulin or [125I]glucagon was detectable. GLP-1-(7-36) amide receptor mRNA was only detected in parietal cell-enriched fractions. GLP-1-(7-36) amide, oxyntomodulin and glucagon stimulated parietal cell cAMP production to similar maximal levels with median values close to 0.28 nM, 10.5 nM and 331.7 nM, whereas oxyntomodulin[19-37] had no effect. The maximal cAMP production induced by GLP-1-(7-36) amide, oxyntomodulin or glucagon was additive to that induced by histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Gros
L
L
INSERM U376, CHU Arnaud-de-Villeneuve, Montpellier, France.
Hollande
F
F
Thorens
B
B
Kervran
A
A
Bataille
D
D
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D000242:Cyclic AMP / Q000096:biosynthesis; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D053772:Oxyntomodulin; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D013004:Somatostatin / Q000494:pharmacology
D053772:Oxyntomodulin; D010446:Peptide Fragments; D012333:RNA, Messenger; D000632:Aminopyrine; C055453:glucagon-like peptide 1 (7-36)amide; D013004:Somatostatin; D004763:Glucagon-Like Peptides; D006632:Histamine; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP