Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In enzymatically dispersed enriched rat parietal cells we studied the effect of pertussis toxin on prostaglandin E2 (PGE2)- or somatostatin-induced inhibition of H(+)-production. Parietal cells were incubated in parallel in the absence (control cells) and presence of pertussis toxin (250 ng/ml; 4 h). [14C]Aminopyrine accumulation by both pertussis toxin-treated and control cells was used as an indirect measure of H(+)-production after stimulation with either histamine, forskolin or dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) alone and in the presence of PGE2 (10(-9)-10(-7) M) or somatostatin (10(-9)-10(-6) M). PGE2 inhibited histamine- and forskolin-stimulated [14C]aminopyrine accumulation but failed to alter the response to dbcAMP. Somatostatin was less effective and less potent than PGE2 in inhibiting stimulation by histamine or forskolin and reduced the response to dbcAMP. Pertussis toxin completely reversed inhibition by both PGE2 and somatostatin on histamine- and forskolin-stimulated H(+)-production but failed to affect inhibition by somatostatin of the response to dbcAMP. After incubation of crude control cell membranes with [32P]NAD+, pertussis toxin catalysed the incorporation of [32P]adenosine diphosphate (ADP)-ribose into a membrane protein of molecular weight of 41,000, the known molecular weight of the inhibitory subunit of adenylate cyclase (Gi alpha). Pertussis toxin treatment of parietal cells prior to the preparation of crude membranes almost completely prevented subsequent pertussis toxin-catalysed [32P]ADP ribosylation of the 41,000 molecular weight protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin reverses prostaglandin E2- and somatostatin-induced inhibition of rat parietal cell H(+)-production. 135 83

Acid secretion from isolated rabbit gastric parietal cells can be stimulated by gastric secretagogues, histamine (cyclic-AMP pathway) and carbachol (inositol phosphate pathway). Prostaglandins (PG) from E series are potent inhibitors of acid secretion. The intracellular mechanism of this inhibition was examined by using a stable PGE1-analogue, misoprostol. Aminopyrine (AP) accumulations due to histamine, IBMX and forskolin were dose-dependently inhibited by misoprostol, whereas a weak but significant biphasic effect on carbachol-induced AP accumulation was observed. The cyclic-AMP formation induced by histamine and IBMX were also inhibited by misoprostol in a non-competitive way. The potent effect of forskolin on cyclic-AMP levels was not modified by misoprostol in parietal cells, whereas it was potentiated in non-parietal cells. The inhibitory effect of misoprostol on AP accumulation was reduced by incubation of parietal cells with Bordetella pertussis toxin (IAP) but not with Cholera toxin (CT). Pretreatment of the cells with IAP did not alter cyclic-AMP levels of resting and histamine-stimulated parietal cells but abolished the inhibitory effect of misoprostol. Treatment with CT increased basal and histamine-stimulated cyclic-AMP levels and masked the inhibitory effect of misoprostol. The biphasic effect of misoprostol on carbachol-stimulated AP accumulation in parietal cells was confirmed on carbachol-stimulated phospholipase C activity and on [Ca2+]i stimulated by carbachol. These data confirm a direct and specific effect of the prostanoid on the Gi-subunit of the adenylate cyclase coupled to the histamine H2-receptor, and a biphasic effect on the phospholipase C pathway of the parietal cells.
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PMID:Intracellular coupling of prostaglandin inhibition of acid secretion in isolated rabbit gastric parietal cells. 169 50

Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on [14C]aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. [14C]Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated [14C]aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on [14C]aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased [14C]aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.
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PMID:Effect of adenosine and adenosine analogs on [14C]aminopyrine accumulation by rabbit parietal cells. 255 91

Adrenergic stimulation of the adenylate cyclase (AC)-cAMP-system and 14C-aminopyrine accumulation, an indirect measure of parietal cell H+-production, was studied in a different preparations of gastric mucosal cells. The beta 2-adrenoceptor agonist hexoprenaline activated AC of crude homogenates from the gastric corpus of mouse, rat, guinea-pig, hog, dog and man. In isolated rat gastric cells (20% parietal cells), treated by low power sonication, 10(-8) to 10(-3) mol/l adrenaline and hexoprenaline activated AC equally potently and efficaciously by maximally 170%. Isoprenaline proved to be less effective activating up to 80%. 5.10(-5) mol/l GMP-PNP augmented basal activity 8.5 times and reduced the maximal efficacy. Adrenaline and hexoprenaline activated AC by maximally 120%, isoprenaline by 40%. The potency of adrenaline was 4 times lower, that of hexoprenaline 2 and that of isoprenaline 4 times higher in the presence of GMP-PNP. Adrenergic stimulation was inhibited by the beta-adrenoceptor antagonist propranolol, the effect of alpha-adrenoceptor-blockade by phenoxybenzamine was less pronounced. In fractions with 7-80% of parietal cells, prepared by isopycnic centrifugation with Percoll, adrenaline and hexoprenaline activated AC or hexoprenaline enhanced the cellular levels of cAMP in parietal cell poor and rich fractions. The degree of activation in response to histamine correlated with the number of parietal cells. 14C-Aminopyrine uptake was increasingly stimulated through 10(-8) to 10(-5) mol/l hexoprenaline, maximally by doubling the basal accumulation. 10(-4) mol/l histamine was 8 times more effective. 3.10(-7) mol/l propranolol inhibited the effect of 10(-5) mol/l hexoprenaline by 80%. The data suggest the localization of beta-adrenoceptors (likely beta 2-adrenoceptors) on parietal and other nonidentified gastric cells. At the parietal cell, adrenaline and hexoprenaline initiate activation of AC and hexoprenaline leads to H+-production. The responses are small compared to the effect of histamine. Thus, beta-adrenoceptor agonists exert intrinsic activity in relation to H+-production. Their influence on stimulated secretion of isolated cells remains to be elucidated.
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PMID:Adrenergic stimulation of isolated rat gastric mucosal cells. Effect on adenylate cyclase and 14C-aminopyrine uptake. 712 15

We have previously shown that in highly enriched rat gastric parietal cells the intestinal peptide hormones oxyntomodulin and glucagon-like peptide-2 (GLP-2) compete for receptor-binding with glucagon-like peptide-1 (GLP-1), a potent cAMP-dependent stimulus of H+ production in vitro. It is, however, unknown whether oxyntomodulin and GLP-2 elicit a biological response by interacting with the GLP-1 receptor. Therefore, we used enriched rat parietal cells to investigate the effects of both hormones on the production of cAMP and H+ ([14C]aminopyrine accumulation). Both parameters were stimulated by oxyntomodulin in a concentration-dependent manner. EC50 values were 6.2.10(-8) and 2.5.10(-7) M oxyntomodulin for stimulation of H+ and cAMP production, respectively. The maximally effective concentrations for stimulation of [14C]aminopyrine accumulation and cAMP production were 1.10(-6) and 1.10(-5) M oxyntomodulin, respectively. At these concentrations oxyntomodulin was nearly as effective as 10(-4) M histamine and equally effective as 10(-8) M GLP-1 (7-36)NH2. In the enriched parietal cell preparation there was no immunocytochemical evidence of contaminating D cells. Accordingly, the responses to oxyntomodulin and GLP-1 (7-36)NH2 were not augmented by incubating the cells in the presence of a polyclonal anti-somatostatin antibody. [14C]Aminopyrine accumulation in response to oxyntomodulin was inhibited by the GLP-1 (7-36)NH2 receptor antagonist, exendin (9-39)NH2, but not by the H2-receptor antagonist, ranitidine. Oxyntomodulin and carbachol acted additively to stimulate [14C]aminopyrine accumulation. GLP-2 (10(-7) to 10(-5)M) was without effect on basal H+ and cAMP production; however, at 10(-5) M GLP-2 markedly inhibited oxyntomodulin-stimulated [14C]aminopyrine accumulation. It is concluded that, by interacting with parietal cell receptors for GLP-1 (7-36)NH2, oxyntomodulin, but not GLP-2, directly stimulates H+ production by activating the adenylate cyclase.
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PMID:Oxyntomodulin: a cAMP-dependent stimulus of rat parietal cell function via the receptor for glucagon-like peptide-1 (7-36)NH2. 891 1