GLP-1-(7-36) amide, -(1-37), and -(1-36) amide: potent cAMP-dependent stimuli of rat parietal cell function.
We investigated the effect of glucagon-like peptide 1 (GLP-1)-(7-36) amide and its molecular variants GLP-1-(1-37) and GLP-1-(1-36) amide on enzymatically dispersed enriched rat parietal cells using [14C]aminopyrine accumulation as a measure of H+ production. GLP-1-(7-36) amide was 100 times more potent than GLP-1-(1-37) and GLP-1-(1-36) amide in stimulating [14C]aminopyrine accumulation. At their maximally effective concentrations, GLP-1-(7-36) amide (10(-8) M), GLP-1-(1-37) (10(-6) M), and GLP-1-(1-36) amide (10(-6) M) reached 80-90% of the response to 10(-4) M histamine. However, the peptides were 100-10,000 times more potent than histamine, which induced maximal [14C]aminopyrine accumulation at 10(-4) M. Stimulation by GLP-1 was dependent on the presence of a phosphodiesterase inhibitor and was not altered by pertussis toxin. Ranitidine failed to affect the response to the GLP-1 variants. Stimulation of H+ production by GLP-1 was accompanied by an increase in the formation of adenosine 3',5'-cyclic monophosphate (cAMP) but not by changes in phosphoinositol breakdown. In stimulating [14C]aminopyrine accumulation, the GLP-1 variants acted additively to threshold but not to maximal concentrations of histamine, suggesting that histamine and GLP-1 activate the same cAMP pool. In contrast, in anesthetized rats GLP-1-(7-36) amide (10-500 ng.kg-1.h-1) had no effect on basal and pentagastrin-stimulated acid secretion in vivo. We conclude that GLP-1 exerts a direct stimulatory effect on rat parietal cells. This potent effect is mediated by cAMP and is independent of H2 receptors. In vivo direct stimulation by GLP-1 of the parietal cells might be counterbalanced by indirect inhibitory mechanisms that are excluded in the in vitro cell system.
Schmidtler
J
J
Department of Internal Medicine II, Technical University of Munich, Germany.
Schepp
W
W
Janczewska
I
I
Weigert
N
N
Fürlinger
C
C
Schusdziarra
V
V
Classen
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D010446:Peptide Fragments; D010455:Peptides; D010566:Virulence Factors, Bordetella; D000632:Aminopyrine; C061970:glucagon-like peptide 1 (7-36); D005576:Colforsin; D004763:Glucagon-Like Peptides; D003994:Bucladesine; C047872:inositol 2-monophosphate; D006632:Histamine; C055968:glucagon-like peptide 1 (1-37); D052216:Glucagon-Like Peptide 1; D002217:Carbachol; D005934:Glucagon; C055454:glucagon-like peptide 1 (1-36)amide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D015056:1-Methyl-3-isobutylxanthine