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:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of aminergic receptors in mouse Ehrlich ascites tumor cells was studied. L-Isoproterenol in vitro stimulated the formation of cAMP in isolated Ehrlich ascites tumor cells. Stimulation by isoproterenol of cAMP formation was not significantly inhibited by practolol, a beta1-adrenoceptor antagonist-Salbutamol, a beta2-adrenoceptor agonist, markedly stimulated the formation of cAMP in Ehrlich ascites tumor cells at concentrations from 10(-8)-10(-3) M. After the addition of salbutamol, cAMP levels reached a maximum in 10 min and declined to about 2-fold of the basal level to 30 min. The stimulation by salbutamol of cAMP formation was markedly inhibited by butoxamine, a beta2-adrenoceptor antagonist, but not by practolol. Furthermore, the effect of a maximal dose of salbutamol was additive to that of prostaglandin E2. Histamine and 4-methylhistamine, a histamine H2 receptor agonist, had no significant effects. Therefore, it is suggested that a beta2-adrenergic receptor exists in the membranes of Ehrlich ascites tumor cells in terms of the adenylate cyclase-cAMP system.
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PMID:Evidence for activation by beta2-adrenergic receptors of adenosine 3',5'-monophosphate formation in Ehrlich ascites tumor cells. 21 68

The action of protein kinase C on the stimulation of adenylate cyclase activity by the histamine H2 receptor was investigated in rat parietal cells. Protein kinase C was activated by preincubating cells with 12-O-tetradecanoylphorbol 13-acetate (TPA), and adenylate cyclase activity was measured in sonicated extracts. TPA (100 nM) inhibited adenylate cyclase activity stimulated by histamine (100 nM-500 microM). This effect was related to the concentration of TPA. TPA (100 nM) enhanced the stimulation of adenylate cyclase activity by forskolin (100 microM) but had no effect on the stimulation by NaF (10 mM). In conclusion, protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor. This action could be mediated by changes in the number of affinity of histamine H2 receptors or in the coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit Gs.
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PMID:Protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor in rat parietal cells. 145 78

Histamine H2 receptor (H2R) has been shown to be coupled to adenylate cyclase. However, we have previously demonstrated that H2R-specific stimulation also activated phospholipase C in human HL-60 promyelocytic leukemia cells (Mitsuhashi M. et al. J. Biol. Chem. 264:18356, 1989). We have extended these studies on HL-60 cells to investigate whether histamine-bovine serum albumin conjugates (HA-BSA) specifically recognize H2R and activate phospholipase C pathways. Both histamine (HA) and HA-BSA increased intracellular concentrations of calcium in a H2R specific manner. However, HA-induced calcium mobilization was transient and returned to the basal level within 1-2 min, whereas HA-BSA-induced calcium mobilization was sustained for more than 10 min as a result of the additional influx of extracellular calcium. More interestingly, fluorescein (FITC) labeled HA-BSA was less incorporated into cytosols and present in the membrane fractions for more than 60 min, whereas membrane-bound FITC-HA was rapidly incorporated into cytosols. Furthermore, the levels of inositol 1,3,4,5-tetrakisphosphate, which is known to activate calcium channels were more sustained after HA-BSA stimulation than those of HA alone. These data suggest that H2R activation mechanism is more complex and may be modified by this slowly metabolized "compound ligand".
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PMID:Multiple signaling pathways of histamine H2 receptors. 190 5

Both the effect of imidazoline derivatives on acid secretion and the mechanism of this effect were studied in the parietal cells isolated from guinea pigs. Clonidine and tolazoline both stimulated the parietal cells to elevate the concentration of cyclic AMP and the accumulation of [14C]aminopyrine concentration dependently, although these imidazoline derivatives are known as alpha 2-adrenoceptor agonist or antagonist. These stimulatory effects were inhibited by famotidine, ranitidine and cimetidine, histamine H2 receptor antagonists. However, [3H]clonidine binding to the membrane preparations of parietal cells was not affected by these H2 antagonists and yohimbine but was inhibited by imidazoline derivatives. These results suggest that imidazoline derivatives may bind to the specific binding sites (different from H2 receptor or alpha 2-adrenoceptor) and stimulate the acid secretion of parietal cells with an increase of cyclic AMP, and that H2 antagonists may not only compete with the agonists for receptor binding but also interfere with the receptor adenylate cyclase system.
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PMID:Effects of histamine H2 receptor antagonists on acid secretion stimulated by imidazoline derivatives in isolated parietal cells. 244 55

Gastric acid secretion was studied in anesthetized rats from day 6 of the postnatal period up to the time of weaning. Basal H+ secretion was detected from day 6 in the first group studied (2.4 +/- 0.2 muEq of H+/10 min/100 g of body weight, BW) and remained constant up to the time of weaning (day 18: 2.5 +/- 0.2 muEq of H+/10 min/100 g of body weight) except for the period between days 10 and 12, when it fell significantly (1.5 +/- 0.06 muEq H+/10 min/100 g of BW on day 12). Both histamine H2 receptor sensitivity and intracellular transduction mechanism activities were evaluated by studying the secretory responses to histamine, impromidine (an H2 receptor agonist), cimetidine (an H2 receptor antagonist), forskolin (a direct adenylate cyclase activator), and dibutyryl (db) cAMP (an analogue of cAMP, the intracellular messenger mediating the response to histamine). The effects of pentagastrin and carbachol were also determined. The secretory responses obtained on days 6, 8, and 18 were similar and represented about threefold increases over basal secretion for all the secretagogues used. After weaning on day 20, both the basal secretion and the response to secretagogues were significantly increased compared with those of unweaned animals. On day 12, the responses were always weaker than on both days 8 and 18. Injection of 1 mg/kg of corticosterone 21 acetate daily from day 8 resulted on day 12 in a basal secretion and a response to histamine equivalent to those measured in 18-day-old pups not injected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of acid secretory function in the rat stomach: sensitivity to secretagogues and corticosterone. 255 Jun 2

In order to analyze the complex activities of histamine H2 receptor activation on neutrophils, human HL-60 promyelocytic leukemia cells were differentiated into neutrophils by incubation with dimethyl sufoxide, loaded with the Ca2+-sensitive indicator dyes, indo-1 or fura-2, and the levels of intracellular Ca2+ ([Ca2+]i) measured in a fluorescent-activated cell sorter and fluorimeter, respectively. Histamine increased [Ca2+]i in a dose-dependent manner with a half-maximal concentration (EC50) of approximately 10(-6) to 10(-5) M, which exhibited H2 receptor specificity. Prostaglandin E2 and isoproterenol also induced [Ca2+]i mobilization in HL-60 cells, whereas the cell permeable form of cAMP and forskolin failed to increase [Ca2+]i. Since H2-receptor mediated [Ca2+]i mobilization was not inhibited by reducing the concentration of extracellular Ca2+ nor by the addition of Ca2+ channel antagonists, LaCl3 and nifedipine, [Ca2+]i mobilization is due to the release of Ca2+ from intracellular stores. Furthermore, both 10(-4) M histamine and 10(-6) M fMet-Leu-Phe increased the levels of 1,4,5-inositol trisphosphate. However, histamine-induced mobilization of [Ca2+]i was inhibited by cholera toxin but not by pertussis toxin, whereas the action of fMet-Leu-Phe was inhibited by pertussis toxin but not by cholera toxin. These data suggest that H2 receptors on HL-60 cells are coupled to two different cholera toxin-sensitive G-proteins and activate adenylate cyclase and phospholipase C simultaneously.
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PMID:Multiple signaling pathways of histamine H2 receptors. Identification of an H2 receptor-dependent Ca2+ mobilization pathway in human HL-60 promyelocytic leukemia cells. 255 5

Histamine induced a concentration-dependent increase in intracellular cyclic-AMP of the two human melanoma cell lines SK23 and DX3.LT5.1; maximal stimulation was obtained with 17.8 microM histamine which consistently produced greater than 50-fold increases in the cyclic AMP content of both cell lines. The dose-response curve for histamine in each culture was progressively displaced to the right with increasing concentrations of the histamine H2 receptor antagonist cimetidine. Ranitidine, another H2 receptor antagonist also prevented the histamine-induced cyclic AMP elevation, but the H1 receptor antagonists mepyramine and tripelennamine had no significant effect. These findings indicate that human melanoma cells express histamine H2 receptors, stimulation of which activates adenylate cyclase with a subsequent rise in intracellular cyclic AMP. Mast cell:melanoma interactions mediated by histamine in vivo might therefore be expected to modify some aspects of melanoma cell behaviour.
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PMID:Demonstration of histamine H2 receptors on human melanoma cells. 283 90

Cells were isolated by use of collagenase, EDTA and pronase form human gastric mucosa obtained at peptic ulcer surgery (n = 61) or at Whipple's operations (n = 6). Enriched parietal cell fractions were prepared by isopycnic centrifugation with Percoll. H+ production, intracellular instrinsic factor and histamine content were maximal in the low density fraction containing 75% parietal cells and--among other nonparietal cell types--mast cells. H+ production, intrinsic factor secretion and adenylate cyclase-activity responded to histamine stimulation in a concentration dependent manner. Response was blocked by histamine H2 receptor antagonists (rantidine, famotidine). Dibutyryl cAMP and the phosphodiesterase inhibitor IMX were the most powerful stimuli whereas carbachol, hexoprenaline and pentagastrin were less effective. Prostaglandin E2 and 6-keto-PGF2 alpha occurred in the highest concentrations in the low density cell fraction. PG production increased linearly for 15 min and seemed to be influenced by the intracellular calcium level.
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PMID:[Isolated human gastric mucosa cells--studies on physiologic and pharmacologic regulatory mechanisms]. 286 82

Isolated canine parietal cells were used to study the ability of misoprostol to inhibit acid secretion in the presence of a number of acid secretagogues. Misoprostol inhibited histamine-stimulated acid secretion in a dose-dependent and noncompetitive manner. A concentration of 2-3 X 10(-9) M misoprostol inhibited maximal histamine-stimulated acid secretion by one half. Misoprostol had little to no effect on acid secretion stimulated by carbachol and dibutyryl cAMP, had no effect on the acid secretion directly stimulated by pentagastrin, and only modestly inhibited acid secretion stimulated by forskolin. Misoprostol noncompetitively inhibited cAMP formation in response to histamine, with an IC50 value similar to that for the inhibition of histamine-stimulated acid secretion. These results indicate that: (1) misoprostol specifically inhibits histamine-stimulated acid secretion in parietal cells, and (2) the antisecretory action of misoprostol is closely related to the reduction of histamine-stimulated cAMP formation with the site of major action most likely in the coupling process between histamine H2 receptor sites and histamine-sensitive adenylate cyclase.
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PMID:Effect of misoprostol on histamine-stimulated acid secretion and cyclic AMP formation in isolated canine parietal cells. 304 Mar 57

The rationale for the present study was to compare calcitonin and gastric inhibitory polypeptide (GIP) versus two histamine H2 receptor antagonists with respect to their potency of inhibiting parietal cell functions. Adenylate cyclase activity and acid production ([14C]aminopyrine uptake) of isolated rat parietal cells were stimulated by histamine. At 10(-7) and 10(-6) mol/l, calcitonin and GIP reduced the response to histamine by 10-20% following noncompetitive kinetics. Ranitidine and famotidine (MK 208) inhibited the response to histamine by about 50% at 10(-7)-10(-6) mol/l, and at 10(-5) mol/l abolished the histamine effect. On a molar basis famotidine turned out to be 6 times more potent than ranitidine. Both antagonists revealed competitive kinetics. Our data suggest direct inhibition of the parietal cells by the tested compounds which were shown to interfere at the adenylate cyclase cAMP system or at the histamine H2 receptor. However, compared to the histamine H2 receptor antagonists, hormonal inhibition is less pronounced and mediated by a different mechanism.
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PMID:Effects of hormones (calcitonin, GIP) and pharmacological antagonists (ranitidine and famotidine) on isolated rat parietal cells. 408 29


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