Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular mechanisms underlying the actions of antisecretory agents were studied with dispersed canine fundic cells; aminopyrine accumulation monitored parietal cell (PC) function. Canine PC have pharmacologically typical histamine (H) H2 and muscarinic (M) receptors. PC also have gastrin (G) receptors, which were selectively blocked by gastrin/CCK antagonists. Potentiating interactions occurred between secretagogues, one of the components of the interdependency between regulatory pathways. Prostaglandins (PG) E2 inhibited H-stimulated PC function. Treatment of PC with pertussis toxin (PT), which inactivates the inhibitory GTP-binding protein of adenylate cyclase (Gi), markedly reduced PG inhibition, indicating PG action via Gi. PC function can also be directly inhibited by H+/K+-ATPase inhibitors, such as omeprazole. When canine mucosal cells were studied, stimulatory G and inhibitory M receptors were present on fundic somatostatin (S) cells. Histamine was localized to canine fundic mast cells, which lacked G or M receptors, a conclusion that may not pertain to fundic histamine cells in other species. Nonparietal cell receptors may be important modulators of the regulation of acid secretion.
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PMID:Mechanisms of action of antisecretory drugs. Studies on isolated canine fundic mucosal cells. 288 44

The mechanism of stimulatory action of histamine on gastric alkaline secretion was investigated in anesthetized rats. Intravenous infusion of histamine (2-8 mg/kg/hr) dose-dependently stimulated acid secretion and in the presence of omeprazole (60 mg/kg), an H+/K+-adenosine triphosphatase inhibitor, produced an increase of gastric but not duodenal alkaline secretion; the degree of gastric alkalinization was also dependent on the dose of histamine, reaching the maximal values of approximately 1.0 microEq/10 min. Cimetidine (100 mg/kg s.c.) significantly inhibited both acid and alkaline secretory responses caused by histamine, whereas indomethacin (5 mg/kg s.c.) significantly prevented the increased alkaline secretion caused by histamine as well as mucosal acidification (100 mM HCl for 10 min). Tripelennamine (10 mg/kg s.c.) had no effect on either acid or alkaline secretion. Histamine (8 mg/kg/hr) reduced the arterial blood pressure (25.3%) and increased the mucosal vascular permeability in the stomach as determined by Evans blue (160%), but these vascular responses were significantly prevented only by tripelennamine, excluding the possible contribution of the vascular effects to the increased gastric alkaline secretion. These results suggest that histamine may stimulate gastric alkaline secretion as well as acid secretion, and the mechanism of histamine-induced alkaline secretion may involve both endogenous prostaglandins and stimulation of H2-receptors.
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PMID:Stimulation of gastric alkaline secretion by histamine in rats: possible involvement of histamine H2-receptors and endogenous prostaglandins. 291 81

A new model for measuring gastric secretory parameters in awake guinea pigs is described. A chronic cannula was surgically implanted in the stomach of each guinea pig. The rates of gastric secretion and changes in intragastric volume were measured using a dye dilution technique. In contrast to previous techniques in small laboratory animals, there was no collection of gastric juice via drainage, no oral intubation for aspiration was involved, no special or sophisticated equipment was used, no anesthesia was employed, and there was no stress associated with acute surgery. This method offers a valuable advantage by combining the chronic gastric cannula with a dye dilution technique in that the same animal can be used several times and finally, several gastric secretory parameters can be measured simultaneously. The animals were used from 3 weeks to 10 months after surgery and as many as 15 studies were performed on the same guinea pig. Samples were collected at 10-min intervals and analyzed for acid and dye concentration from which the onset and kinetics of gastric secretion were followed. Basal gastric secretion (11.8 +/- 1.6 mueq/kg/min; all mean +/- 1 SEM) was increased within 20 min after subcutaneous infusion of histamine (30 micrograms/kg/hr) and peaked by 40-60 min at a mean acid output rate of 41 +/- 3 mueq/kg/min. Histamine also increased the intragastric volume from 6.3 to 13.4 ml as it increased fluid output from 1.6 +/- 0.1 ml/10 min to 3.4 +/- 0.2 ml/10 min. The increase in acid output caused by histamine was inhibited by the H2-antagonists cimetidine (3 mumole/kg) and ranitidine at 0.5 mumole/kg. Omeprazole (1.2 mumole/kg), an H-K-ATPase inhibitor, almost abolished acid output under both basal and histamine-stimulated conditions. Thus, the present method is simple and suitable to study the physiology and pharmacology of gastric secretion in the guinea pig with a particular emphasis on the action of histamine. Furthermore, because of the species involved, there is also a significant economical advantage and the guinea pig can also be used as a potential model for studying experimental ulcer.
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PMID:A new in vivo method for repeatedly studying gastric acid secretion and other secretory parameters in awake guinea pig. 331 43

Dogs provided with a gastric fistula were treated orally for 1 week either with the H+, K+-ATPase inhibitor omeprazole, 80 mumol/kg once daily, or with the histamine H2 receptor antagonist ranitidine, 85-175 mumol/kg every 8 h. Acid secretion, serum gastrin levels and [3H]-thymidine incorporation in the corpus mucosa were determined before, during and after the treatment period. In order to examine differences between species, plasma gastrin levels and [3H]-thymidine incorporation in the oxyntic mucosa were also determined in female rats treated up to 1 week with omeprazole, 400 mumol/kg orally once daily. Histamine-stimulated gastric acid secretion in dogs treated with omeprazole or ranitidine was almost completely inhibited during the whole treatment period. As a consequence of that, the meal-stimulated gastrin levels were increased (7-fold) during treatment by both compounds. [3H]-thymidine incorporation in the dog corpus mucosa was increased approximately 4 times on day 5 both with omeprazole and ranitidine. After the treatment was stopped, gastric acid secretion, serum levels of gastrin and the rate of [3H]-thymidine incorporation were back to control level in both groups within 11 days. In the rats, the plasma gastrin levels increased 10-fold and the rate of [3H]-thymidine incorporation in the corpus mucosa increased 3-fold during treatment with omeprazole. In conclusion, a pronounced suppression of gastric acid secretion over the day with antisecretagogues results in hypergastrinemia in both dogs and rats. As a consequence of the trophic effect of gastrin, the incorporation of [3H]-thymidine in the oxyntic mucosa is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of omeprazole and ranitidine on gastric acid secretion, blood gastrin levels and [3H]-thymidine incorporation in the oxyntic mucosa from dogs and rats. 341 Jan 71

The interaction between histamine and various antisecretagogues acting by different mechanisms has been investigated in the isolated fundus from the rat stomach. Histamine evoked a concentration-dependent stimulatory effect which was competitively antagonized by the H2-receptor antagonist, ranitidine and non competitively by the H+/K+-ATPase inhibitor, omeprazole. The histamine induced secretion was highly resistant to the action of the calcium entry blocker verapamil, somatostatin and KSCN, but some inhibition was obtained with the calmodulin antagonist, trifluoperazine. Removal of calcium ions from the bathing media (both mucosal and serosal) greatly enhanced histamine-induced gastric secretion. The results suggest that the relationship between receptor stimulation and the intracellular events leading to acid secretion is far from being elucidated.
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PMID:Rat gastric secretion "in vitro": interaction between histamine and various antisecretagogues acting by different mechanisms. 408 8

The effect of bivalent cations on NaCl-stimulated ATPase activity in rabbit small intestinal mucosa was studied. Unlike Ba2+ and Zn2+, Ca2+ and Mg2+ added to the incubation medium at a concentration of 0.25 mM completely change ATPase activity. Histamine considerably reduces the inhibitory effect of Ca2+ and Mg2+ on NaCl-stimulated and oligomycin-inhibited ATPase activity. Possible mechanisms of the enzyme activity control in the cell are discussed.
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PMID:[Effect of divalent cations on the properties of NaCl-stimulated ATPase activity in the mucosa of the rabbit small intestine]. 621 73

The effect of histamine on Mg-ATPase was assessed in homogenates of gastric biopsies taken from the body and antrum of the stomach of patients with and without duodenal ulcer (DU). Histamine at concentrations greater than 10(-7) mol/l caused significant activation of this crude enzyme activity in the body mucosa from both groups of patients; maximum stimulation of enzyme activity was greater in the DU patients than in the non-DU group. No activation by histamine was found in ATPase of antral biopsies. Administration of cimetidine (1 g/day orally) to DU patients for 28 days abolished the histamine activation of the enzyme activity. Investigation of the activity of enzymes in normal biopsies showed that the effect of histamine was not shared by the specific H2 agonist, impromidine, or H1 agonist, 2-(2-aminoethyl)-thiazole, and that cimetidine inhibition of ATPase in vitro is probably not an histamine-receptor-specific effect.
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PMID:Effect of cimetidine on histamine-activated ATPase in human gastric mucosa. 621 29

1 RMI 12330A, a lactam-imine, at concentrations of 10(-4) M and higher, inhibited basal as well as isoprenaline and NaF-stimulated adenylate cyclase activity of guinea-pig heart homogenates. However, RMI 12330A was a more potent inhibitor of histamine-stimulated adenylate cyclase (IC50 of 1.5 X 10(-5) M). 2 In the isolated work-performing heart of the guinea-pig, RMI 12330A (IC50 of 1.1 X 10(-6) M) depressed all cardiac functions: pressures developed, dP/dt, contractile force, dF/dt, work performance and stroke work. Left atrial pressure rose and the positive inotropic response to increasing heart rate (staircase) became negative. Histamine, isoprenaline and ouabain no longer caused positive inotropic effects. 3 Increasing the perfusate calcium concentration from 2.5 mM to 4.5 and 6.5 mM completely restored cardiac function after its depression by RMI 12330A. 4 RMI 12330A uncoupled mitochondrial oxidative phosphorylation; the classical uncoupler, dinitrophenol, had the same effects on cardiac dynamics as RMI 12330A. 5 RMI in high doses inhibited hydrolytic activity of Na+, K+-ATPase of crude and purified heart preparations (IC50 of 1.7 X 10(-4) M) and inhibited ouabain binding to the same enzymes (IC50 of 1.5 X 10(-4) M). 6 A lactam-imine analogue of RMI 12330A that had no effect on adenylate cyclase, was also without effect on any of the systems examined.
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PMID:Effects of RMI 12330A, a new inhibitor of adenylate cyclase on myocardial function and subcellular activity. 625 99

The light and heavy smooth-surfaced membranes (LSM and HSM), which had densities corresponding to 1.08 M and 1.28 M sucrose, respectively, were isolated from rat brain and some of their biochemical properties were investigated. Both LSM and HSM showed high Na+,K+-ATPase activity and, in particular, in HSM the activity was four times (21.55 mumol/mg protein/h) higher than that of the brain homogenate. High 2',3'-cyclic nucleotide 3'-phosphodiesterase activity (293.4 mumol/mg protein/h) was characteristic of LSM. 5'-Nucleotidase and acetylcholinesterase activities were also higher in LSM than in HSM. SDS-polyacrylamide gel electrophoresis showed that LSM and HSM had many protein component and that low molecular weight proteins such as proteolipid protein and basic protein were almost absent, in contrast with myelin and myelin-like membrane. GM1 ganglioside constituted the major class of total ganglioside in both LSM and HSM. These biochemical findings suggested that LSM is a membrane that has not previously been described, or a membrane fraction related to the oligodendroglial plasma membrane.
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PMID:Further studies on the smooth-surfaced membranes isolated from rat brain. 625 69

A great deal of knowledge has been gained concerning the activation of adenylate and guanylate cyclase in epidermal cells. Adenylate cyclase is activated by 4 different independent receptors-responding respectively to catecholamine (beta), to prostaglandins (E), to histamine (H2), and to adenosine and it phosphorylated derivatives. Upon activation, each of these receptors becomes unresponsive to further stimulation by its specific stimulator. Guanylate cyclase, on the other hand, is activated by histamine (H1) and epidermal growth factor (EGF). Unlike EGF, the histamine activation is extremely rapid (less than 5 minutes). Epidermal cells are permeable (leak) to cyclic GMP but not cyclic AMP. When the skin is traumatized or injured in any way (even by intradermal injection) there is a sudden catastrophic change in the intracellular levels of the cyclic nucleotides (and of ATP). Cyclic AMP rapidly rises to perhaps 5-10 times its normal resting level while cyclic GMP falls to 10-20% of its level in vivo. The rise in cyclic AMP is due to activation of adenylate cyclase while the fall in cyclic GMP is due in major part to activation of cyclic GMP phosphodiesterase (and perhaps the fall in ATP is due to activation of ATPase). The changes in ATP and cyclic AMP can be reversed by incubating the tissue in a buffered salt solution containing glucose, but this does not normalize the cyclic GMP content. The fall in cyclic GMP can be prevented by a phosphodiesterase inhibitor (IBMX ). This series of events has been called the "ischemia effect." However, it implies that a lack of oxygen is at fault, and that has not been shown to be the case. Its underlying cause and possible physiologic significance are not known. Do these changes in cyclic nucleotides have effects on epidermal proliferation? And does EGF? Agents which increase cyclic AMP do inhibit the epidermal outgrowth and mitotic activity of explant cultures of pig skin. Cyclic GMP does increase outgrowth at a particular concentration. Histamine, which elevates both cyclic nucleotides, has a biphasic action depending on its concentration. These findings imply that these nucleotides do act as one of the controls of epidermal proliferation. The action of cyclic GMP is not accompanied by detectably increased phosphorylation of epidermal proteins. On the other hand, EGF action which also enhances epidermal outgrowth is characterized by an increased protein phosphorylation that precedes any increase in cellular cyclic GMP. We conclude that the action of EGF is independent of the cyclic nucleotide system.
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PMID:Cyclic GMP system in the epidermis. 626 50


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