Inhibitory action of extracellular adenosine 5'-triphosphate on parietal cells isolated from rabbit gastric mucosa.
The effects of the purine nucleotides, adenosine 5'-triphosphate (ATP) and their analogs 2-methylthio ATP and beta, gamma-methylene ATP, as well as those of the pyrimidine nucleotide, uridine 5'-triphosphate (UTP), on acid production in isolated rabbit gastric parietal cells prepared by enzymatic dispersion and enriched by counterflow elutriation were studied. The (14C)-aminopyrine (AP) accumulation method was used as an index of acid production by the parietal cells. In histamine-stimulated parietal cells, ATP and 2-methylthio ATP, but not beta, gamma-methylene ATP or UTP, produced significant and concentration-related inhibition of the histamine-stimulated AP uptake. The rank order of potency of these nucleotides in inhibiting histamine-stimulated AP accumulation was 2-methylthio ATP > ATP > > beta, gamma-methylene ATP, UTP. In contrast to these results, the AP accumulation responses to secretagogues other than histamine such as carbachol and dibutyryl-cAMP, were not significantly modified by ATP and analogs. Pretreatment of parietal cells with indomethacin, a prostaglandin synthesis inhibitor, led to a significant reduction of the inhibitory responses elicited by ATP on histamine-stimulated AP uptake. These data suggest that ATP selectively inhibits the histamine-stimulated gastric acid secretion in rabbits by acting directly on parietal cells; that a component of this action seems to be related with a stimulation of prostaglandin production; and that the antisecretory effect of ATP on isolated rabbit parietal cells may be mediated via P2Y-purinoceptors.
Gil-Rodrigo
C E
CE
Departamento de Fisiología, Facultad de Medicina, Universidad del País Vasco (UPV-EHU), Bilbao, Spain.
Bergaretxe
I
I
Carou
M
M
Galdiz
B
B
Salgado
C
C
Ainz
L F
LF
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000632:Aminopyrine / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D014544:Uridine Triphosphate / Q000494:pharmacology
D000632:Aminopyrine; D003994:Bucladesine; D006632:Histamine; D000255:Adenosine Triphosphate; D002217:Carbachol; D014544:Uridine Triphosphate; D007213:Indomethacin