RESUMO
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.
Assuntos
Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Células Parietais Gástricas/fisiologia , Aminopirina/farmacocinética , Animais , Transporte Biológico/efeitos dos fármacos , Bucladesina/farmacologia , Carbacol/farmacologia , Histamina/farmacologia , Técnicas In Vitro , Indometacina/farmacologia , Cinética , Células Parietais Gástricas/efeitos dos fármacos , Coelhos , Uridina Trifosfato/farmacologiaAssuntos
Células Parietais Gástricas/metabolismo , Receptores Purinérgicos P2/metabolismo , Animais , Fracionamento Celular , Membrana Celular/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Cinética , Células Parietais Gástricas/ultraestrutura , Coelhos , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
The effect of adenosine 5'-triphosphate (ATP) on gastric acid secretion stimulated by histamine, carbachol and dibutyryl-cAMP (db-cAMP) was studied using glands isolated from rabbit gastric mucosa. The (14C)-aminopyrine (AP) accumulation method was used as an index of acid production by the gastric glands. Histamine-stimulated AP accumulation was significantly inhibited by ATP (10 mumol/l-1 mmol/l). The inhibitory action of ATP appeared to be specific, inasmuch as this nucleotide had no significant effect on basal secretion or secretion stimulated by carbachol or db-cAMP. The antisecretory effect of ATP on histamine-stimulated glands was not affected by the P1-purinoceptor antagonist, theophylline. Pretreatment of glands with indomethacin, a well known prostaglandin synthesis inhibitor, led to a significant reduction of the inhibitory responses to ATP. These results show that ATP inhibits the histamine-stimulated AP accumulation by rabbit isolated gastric glands and suggest that this effect is not due to an ectoenzymatic conversion of ATP into adenosine but to a direct effect of ATP which may be mediated via a P2-purinoceptor subtype linked to prostaglandin production.