COMPARATIVE EFFECTS OF GLP-1-(7-36) AMIDE, OXYNTOMODULIN AND GLUCAGONON 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 r abbit parietal cell-enriched fractions (F3, Mn), with parietal cell co ntents of 60% and 88%, respectively. Histamine (10(-5) M) stimulated [ C-14]aminopyrine accumulation to an amount of 850% in excess of the ba sal level, whereas GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10 (-6) M) induced increases of 50% and 30%, respectively. With a histami ne concentration of 10(-6) M, [C-14]aminopyrine accumulation was stimu lated 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%, res pectively. With these parameters, oxyntomodulin[19-37] and glucagon we re without effect. Specific binding of [I-125]GLP-1-(7-36) amide to pa rietal 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 [I -125]oxyntomodulin or [I-125]glucagon was detectable. GLP-1-(7-36) ami de receptor mRNA was only detected in parietal cell-enriched fractions . GLP-1-(7-36) amide, oxyntomodulin and glucagon stimulated parietal c ell 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, ox yntomodulin or glucagon was additive to that induced by histamine. Our data demonstrate the presence of a GLP-1-(7-36) amide receptor in rab bit parietal cell coupled to the cAMP pathway and the interaction of o xyntomodulin and glucagon with this receptor. The results argue in fav or of a cAMP compartment coupled to the GLP-1-(7-36) amide receptor, d ifferent from that involved in histamine-induced [C-14]aminopyrine acc umulation.