Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of gastrointestinal hormones on electrical and mechanical activity of smooth muscle of cat stomach were studied. Spontaneous electrical activity of the antrum preparation consisted of slow waves with superimposed spike-like potentials. Phasic contractions occurred synchronously with the electrical activity. Pentagastrin, tetragastrin, pancreozymin and secretin increased frequency of slow wave component and amplitude of phasic contraction. Atropine and tetrodotoxin did not block the spike-like potential and slow wave component. Noradrenaline and verapamil blocked the phasic contraction. The excitatory effects of these gastrointestinal hormones were observed in the presence of atropine, tetrodotoxin and dibenamine, but not in verapamil. When the mechanical activity of the antral strips was depressed by caffeine or theophylline, the excitatory effects of gastrointestinal hormones were also suppressed. The excitatory effects produced by these hormones were potentiated by imidazole. These results suggest that gastrointestinal hormones have a direct excitatory action on the longitudinal smooth muscle of the antrum region and that the excitatory action is associated with phosphodiesterase activity and intracellular cyclic AMP content.
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PMID:Effects of gastrointestinal hormones on the electrical and mechanical activity of the cat stomach. 91 66

Rat gastric mucosal cells, containing 25-35% parietal cells, were obtained by a modified isolation procedure involving protease, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and mechanical treatments. Parietal cell responsiveness to secretagogues was assessed by the accumulation of the weak base [14C]aminopyrine in intracellular acidic compartments. Histamine, without phosphodiesterase inhibitors, dose dependently stimulated aminopyrine accumulation with an effective concentration producing 50% of maximal response of 13 microM and a maximal effective dose of 100 microM. Pentagastrin and rat gastrin-17 alone were ineffective but potentiated dose dependently the action of 100 microM histamine. The mean potentiating effect varied from 32 to 70% for 100 nM pentagastrin and from 36 to 95% for 100 nM rat gastrin-17. Pentagastrin (100 nM) also potentiated the effect of 1 mM dibutyryladenosine 3',5'-cyclic monophosphate (cAMP) by 44%, but it did not increase further the stimulation by carbachol. The potentiating effect of pentagastrin on histamine- and dibutyryl cAMP-stimulated aminopyrine accumulation was also observed after enrichment of parietal cells to 65-85%. The endogenous histamine was insufficient to stimulate acid production. Therefore gastrin appears to have a direct action also in rat parietal cells.
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PMID:Gastrin potentiates histamine-stimulated aminopyrine accumulation in isolated rat parietal cells. 165 74

This study was performed to examine the effect of cAMP levels on histamine release in the isolated rat stomach. Pentagastrin-induced histamine release was unaffected by phosphodiesterase inhibition, and pentagastrin itself had no phosphodiesterase-like effect. The results support previous observations showing that histamine is likely to be the mediator of the acid secretagogue effect of (penta) gastrin.
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PMID:Pentagastrin-stimulated histamine release and acid secretion from the totally isolated vascularly perfused rat stomach. 171 Dec 78

Gastric mucosal cells were isolated from resected fundic mucosa of peptic ulcer patients and used to determine H+ production by [14C]-aminopyrine (AP) uptake. H+ production was stimulated by histamine linearly for 40 min and in a concentration-dependent manner reaching a maximum of 228% of basal at 10(-4) mol/l histamine. This response was reduced by the histamine H2-receptor antagonist ranitidine (IC50 = 3 X 10(-6) mol/l). Pentagastrin and carbachol induced a small but significant increase at 10(-7) and 10(-4) mol/l, respectively. At low histamine concentrations the response to carbachol plus histamine was nearly additive. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) was a powerful stimulant of basal AP uptake but failed to augment the histamine effect. IBMX-induced AP uptake was reduced by ranitidine suggesting that, at least in part, the response to IBMX is mediated by release of endogenous histamine. Isopycnic centrifugation with Percoll resulted in fractions with 7 and 72% parietal cells, respectively. Basal AP uptake amounted to 203 cpm/10(6) cells in the parietal cell depleted fraction whereas in the enriched preparation the basal rate (4,787 cpm/10(6) cells) exceeded the uptake which was to be expected due to 10-fold parietal cell enrichment. When calculated as percentage of the basal H+ production the histamine-stimulated AP uptake was less in the enriched fraction than in the parietal cell depleted or in the nonfractionated preparation. Basal AP uptake was reduced by ranitidine more effectively in the enriched fraction suggesting background stimulation by endogenous histamine which might impair the response to exogenous stimulants. This functional evidence was paralleled by electron microscopical identification of mast cells copurified in the enriched parietal cell fraction.
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PMID:[14C]-aminopyrine accumulation by isolated human parietal cells. 242 35

We investigated the hypothesis of a direct effect of amino acids on gastric parietal cells. [14C]aminopyrine uptake into isolated enriched rat parietal cells served as a quantitative index of H+ production. Cells were incubated in media containing 1 mM Ca2+ in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), or 3 mM Ca2+ without IBMX. Under these different conditions, L-arginine, L-phenylalanine and L-tryptophan (10(-6) M to 3 X 10(-2) M) failed to alter basal [14C]aminopyrine uptake as well as the response to submaximal stimulation by histamine, forskolin, N6O2-dibutyryladenosine-3',5'-(cyclic)-phosphate (db cAMP) or carbachol. Pentagastrin failed to elicit an appreciable response in the presence and absence of 10(-3) M of all three amino acids studied. It is concluded that in vivo the potent stimulation of gastric acid secretion by L-arginine, L-phenylalanine and L-tryptophan is mediated by other than direct mechanisms.
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PMID:Effect of amino acids on H+ production by isolated rat parietal cells. 263 96

We tested the hypothesis that the increase in gastric mucosal blood flow during pentagastrin-stimulated acid secretion in the rat is mediated partly by endogenously generated adenosine. In in vivo microscopic studies, topical 10(-5) to 10(-3) M adenosine dose-dependently dilated the submucosal arterioles, the vessels that control mucosal blood flow. The adenosine receptor antagonist 8-phenyltheophylline, significantly reduced adenosine's vasodilatory response. An adenosine analog with a high A2 receptor affinity was 100 times more potent as a vasodilator than one with a high A1 receptor affinity but lower A2 receptor affinity. We then examined the effect of i.v. 8-phenyltheophylline, 10 mg/kg, on the pentagastrin-stimulated increase in gastric blood flow and gastric acid secretion. Mucosal blood flow was estimated by the hydrogen clearance technique. Pentagastrin increased mucosal blood flow from 26.6 +/- 2.6 to 42.7 +/- 4.9 ml/min/100 g and this was reduced to 31.9 +/- 3.1 ml/min/100 g upon the addition of 8-phenyltheophylline. Gastric acid secretion upon the addition of 8-phenyltheophylline. Gastric acid secretion was stimulated by pentagastrin and stimulated further by the addition of 8-phenyltheophylline from 2.06 +/- 0.34 mEq of H+ per min to 2.84 +/- 0.49 mEq/min. 8-Phenyltheophylline had no effect on basal mucosal blood flow or gastric acid secretion. In contrast, the nonmethylxanthine phosphodiesterase inhibitor RO 20-1724 stimulated acid secretion and increased gastric mucosal blood flow during pentagastrin administration. The data suggest that gastric submucosal arterioles contain adenosine receptors of the A2 subtype that vasodilate when activated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of adenosine in the gastric blood flow response to pentagastrin in the rat. 281 Jan 11