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)

We previously demonstrated that treatment with indomethacin in vivo significantly blunted the glucagon-induced glycemic response in the rat. This prostaglandin synthetase (cyclo-oxygenase) inhibitor also accentuated the evanescent effect of glucagon on hepatic glucose output in the intact, anesthetized rat. In this report, we present evidence that impairment of glucagon action in the rat liver by indomethacin is mediated through its inhibitory effect on both cAMP-dependent and cAMP-independent hepatic protein kinase. Indomethacin treatment did not have a measurable effect on any of the other components of the glucagon transducer system. Furthermore, infusion with glucagon for two hours that maintained plasma glucagon values at high physiological levels significantly reduced hepatic cAMP-dependent protein kinase activity without altering its Km. Glucagon infusion also down-regulated its own hepatic receptors and glucagon-stimulated cAMP production; prostaglandin E1-stimulated cAMP production was not affected. We concluded that prostaglandins may play a role in the regulation of hepatic protein kinases involved in the glucagon-stimulated glycogenolytic response and that glucagon-induced down-regulation extends at least to the hepatic protein kinases. However, a direct effect of indomethacin or protein kinase and the adenylate cyclase complex cannot be ruled out.
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PMID:Modulation of hepatic protein kinase activity by indomethacin. 608 43

The effect of drastic sodium chloride changes (performed by using low-Na diet + furanthril and high-Na diet) on renin-angiotensin-aldosterone system, vasopressin and renal prostaglandins was studied in normal subjects after inhibition of prostaglandin synthesis by indomethacin (0.35 mg/kg three times daily for 13 days). The purpose of the investigation was to evaluate the mechanism of prostaglandin-vasopressin interrelationship. Indomethacin inhibition of PG-synthesis was performed, and after high-Na provocation, an increase of vasopressin and cyclic AMP excretion by 15% and 376% more than that without indomethacin was found. Indomethacin by itself caused sodium retention and antidiuretic effect. The results confirmed the assumption that renal prostaglandins are modulators of renin release from the kidney and that they alternate vasopressin effect on urine concentration, most probably through adenylate cyclase-cAMP system.
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PMID:Humoral factors involved in the regulation of sodium-fluid balance in normal man. II. Effect of indomethacin on sodium concentration, renal prostaglandins, vasopressin and renin-angiotensin-aldosterone system. 609 12

We tested the effect of prostaglandins PGF2 alpha and PGE1 on the transport of 36Cl and 22Na by canine tracheal epithelium. Sheets of epithelium were mounted in Ussing chambers and short-circuited. Addition of PGF2 alpha to the mucosal side resulted in an increase of net Cl secretion from 0.71 +/- 0.41 to 2.40 +/- 0.67 mu eq . cm-2 . h-1 without significant effect on net Na absorption. Prostaglandin E1 on the mucosal side increased net Cl secretion from 1.36 +/- 0.31 to 2.69 +/- 0.35 and decreased Na absorption from 0.87 +/- 0.16 to 0.49 +/- 0.09. Indomethacin significantly depressed net Cl secretion from 1.36 +/- 0.36 to 0.57 +/- 0.22. Subsequent addition of PGE1 augmented net Cl secretion to 3.88 +/- 0.75. PGE1 did not enhance [14C]mannitol fluxes across this epithelium. Cellular levels of cAMP increased in response to PGE1 from 130 +/- 12.7 to 642 +/- 33.4 pmol . mg prot-1 . 10 min-1, whereas PGF2 alpha had no effect. These data suggest that although effects of PGF2 alpha and PGE1 are similar as pertains to net Cl secretion, they differ in their effects on Na transport and their capacity to increase cAMP levels. Alterations in Cl and Na transport in response to PGE1 are likely to be mediated, at least in part, by the adenylate cyclase-cAMP system. Furthermore, endogenous prostaglandins may have an important regulatory role in ion transport by airways epithelium.
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PMID:Modification of Na and Cl transport in canine tracheal mucosa by prostaglandins. 625 46

Kupffer cells exposed to bacterial lipopolysaccharide in vitro synthesized collagenase and released the major portion of it into the extracellular space while the intracellular level of enzyme was not altered significantly. Cycloheximide prevented the appearance of collagenase in the medium indicating de novo synthesis. Indomethacin, an inhibitor of cyclooxygenase, also blocked collagenase synthesis. In line with this observation. Kupffer cells were found to synthesize substantial amounts of prostaglandin E2 when exposed to lipopolysaccharide; concomitantly, cellular cAMP levels were increased. Indomethacin was shown to abolish the stimulated cAMP formation. Addition to the culture medium of cAMP or dibutyryladenosine 3', 5'-monophosphate as well as of prostaglandin E2 or, to a lesser extent, prostaglandin E1 allowed indomethacin-inhibited cells to resume the production of collagenase. It is proposed that in rat Kupffer cells lipopolysaccharide-elicited collagenase synthesis and excretion is mediated sequentially by stimulated production of prostaglandin E2, enhanced adenylate cyclase activity and increased intracellular cAMP levels.
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PMID:Involvement of prostaglandin E and adenosine 3', 5'-monophosphate in lipopolysaccharide-stimulated collagenase release by rat Kupffer cells. 628 7

Prolactin possesses positive inotropic actions in isolated heart preparations although the mechanism of this influence is not understood. Our study was designed to investigate the mechanism of this effect on the rat heart. Prolactin (50 ng/ml) produced a time-dependent increase (60%) in contractile force that reached maximum after 30 min and remained steady for a further 30 min. A similar time-dependent phenomenon was seen with 200 ng/ml prolactin although the maximum inotropic effect was reduced. Indomethacin (30 micrograms/ml) significantly reduced the inotropic effect of both prolactin concentrations although the effect of the hormone was not related to the release of 6-keto-PGF1 alpha, the prostacyclin metabolite. Propranolol (1-20 micrograms/ml) significantly reduced the positive inotropic effect of prolactin. Prolactin however had no influence on myocardial adenylate cyclase activity. Hearts that were removed from animals pretreated with 1.25 or 2.50 mg/kg reserpine did not respond to prolactin administration. It is suggested that the inotropic influence of prolactin is mediated by endogenous catecholamine liberation.
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PMID:A possible mechanism of inotropic action of prolactin on rat heart. 629 10

The effects of ethanol on parathyroid hormone (PTH)-induced increases in adenosine 3':5'-phosphate (cAMP) concentrations were studied in renal cortical tubules of hamsters in vitro. Ethanol concentrations between 0.1 and 3% were found to augment the PTH response in a dose-related way while, concentrations greater than 3% produced a dose-related inhibition of the PTH response. In the absence of PTH, ethanol did not significantly elevate cAMP accumulations at any concentrations tested. In contrast to its effect on intact tubule cells, ethanol did not alter either adenylate cyclase or phosphodiesterase in renal cortical homogenates. Indomethacin, however, produced a concentration-related inhibition of the ethanol-potentiated response without altering the effects of PTH alone. The results suggest a possible involvement of prostaglandins in the potentiating effect of ethanol on the PTH-dependent accumulation of cAMP in renal tubules.
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PMID:Enhancement by ethanol of parathyroid-hormone-stimulated cyclic AMP accumulation in isolated renal tubules. 630 64

Isoprenaline, vasoactive intestinal peptide (VIP), prostaglandin E2 (PGE2) and forskolin caused a dose-dependent relaxation of normal and ovalbumin-sensitized guinea-pig tracheal spirals and lung parenchymal strips in vitro. There was no difference in magnitude of relaxation or sensitivity to these relaxants between normal and sensitized tissues. The rank order of potency (concentration of each drug at which 50% of the maximum is obtained) for these relaxants on both trachea and parenchyma was VIP greater than isoprenaline greater than PGE2 greater than forskolin, although the parenchyma was more sensitive than the trachea. The rank order of efficacy of the drugs used in relaxing both the trachea and lung parenchyma was isoprenaline (10 microM) greater than forskolin (30 microM) greater than VIP (0.1 microM) greater than PGE2 (10 microM). PGE2 at concentrations greater than 1 microM sometimes contracted the lung strip. Pretreatment with indomethacin (8.5 microM), a cyclo-oxygenase inhibitor, reduced the resting tone of tracheal spirals, but did not significantly affect the tone of lung strips. Indomethacin-pretreatment did not affect drug-induced relaxations of either normal or sensitized tracheal spirals. However, both normal and sensitized indomethacin-pretreated lung strips relaxed significantly less (P less than 0.05) to isoprenaline, PGE2 and forskolin. Indomethacin-pretreatment did not affect sensitivity of normal and sensitized trachea or parenchyma to the relaxant drugs. All the relaxant drugs used stimulated adenylate cyclase activity in normal or sensitized lung parenchyma membrane preparations. The rank order of efficacy (maximal activation) was forskolin greater than isoprenaline = VIP greater than PGE2. There was no difference in response between normal and sensitized lungs. Adenylate cyclase activity of normal lung was stimulated as follows: forskolin (100 microM), 500.0 +/- 50.0%; isoprenaline (100 microM), 186.0 +/- 29.0%; VIP (10 microM), 213.0 +/- 19.0% and PGE2 (100 microM), 155.0 +/- 23.0% of basal activity. Similar values were obtained for sensitized lung parenchyma. Indomethacin-pretreatment did not significantly affect normal or sensitized lung adenylate cyclase stimulation by isoprenaline, VIP, forskolin or PGE2. It was concluded that: Immunological sensitization to ovalbumin does not induce hypoactivity of relaxant drug receptors and/or the adenylate cyclase system of the airway tissues of the guinea-pig. (b) There is an apparent lack of correlation between tissue relaxation in vitro and adenylate cyclase activity since the rank order of the efficacy of a range of relaxants was different for the two effects and furthermore indomethacin-treatment of airway tissues yielded differential results.
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PMID:Bronchodilator-mediated relaxation of normal and ovalbumin-sensitized guinea-pig airways: lack of correlation with lung adenylate cyclase activation. 643 71

Indomethacin, a rapid and intense inhibitor of prostaglandin synthesis, was used with a view to find out similarity in secretory mechanism of heat-labile enterotoxins of three diarrhoea producing enteric bacteria viz., Salmonella weltevreden, Escherichia coli and Vibrio cholerae in rabbits. A significant inhibition (90% to 94%) of biological activity of indomethacin pretreated Salmonella enterotoxin was evident in indomethacin treated rabbits, whereas the biological activity was found comparatively low (28% to 76%) in the untreated enterotoxin preparations. In contrast, the skin permeability reaction to cholera toxin remained unaltered in the absence of pretreatment of cholera toxin with indomethacin and it dropped to 55% in pre-treated toxin preparations. There was complete inhibition of biological activity of E. coli enterotoxin which did not receive indomethacin pretreatment. Based on these observations it may be inferred that indomethacin inhibits skin permeability response of heat labile enterotoxin of S. weltevreden both by blocking the effect of prostaglandins (Blocking mechanism) as well as by prostaglandin-adenyl cyclase pathway. The reduction in the biological activity of cholera toxin seems to be occurring through blocking of prostaglandins by indomethacin. In case of E. coli enterotoxin the inhibition mechanism seems operating through prostaglandin-adenyl cyclase system. These observations indicate that the Salmonella enterotoxin shares some similarity with enterotoxins of E. coli and Vibrio cholerae in respect of mechanism of action.
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PMID:Inhibitory effect of indomethacin on skin permeability reactions mediated by heat-labile enterotoxins of Salmonella weltevreden, Escherichia coli and Vibrio cholerae. 675 Sep 83

We have investigated the role of prostaglandin E2 (PGE2) in the regulation of cytokine release (IL-2, IL-3 and IFN) by cortico-resistant thymocytes (CRT) stimulated or not through the T-cell antigen receptor by an anti-CD3 monoclonal antibody (mAb). CRT were found to spontaneously produce IL-2 and IL-3 on day 4 of culture, but not IFN. After activation with an anti-CD3 mAb, the maximal levels for IL-2 and IFN were observed on day 1 and for IL-3 on day 4. Addition of PGE2 inhibits IL-2 production and has no effect on IFN production. Indomethacin, an inhibitor of the cyclooxygenase pathway, enhanced both IL-2 and IFN production. In contrast, IL-3 secretion by anti-CD3 activated CRT was up-regulated by PGE2, and its level was decreased in the presence of indomethacin in both stimulated or unstimulated cells. As has been observed with PGE2, forskolin which activates adenylate cyclase increases the IL-3 level. Thus PGE2 may interfere in the process of thymocyte proliferation and/or differentiation by regulating differentially the interleukin production.
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PMID:Regulation by PGE2 of IL-2, IL-3 and IFN production by cortico-resistant thymocytes. 751 Feb 66

Evidence in vivo indicates that endogenous and exogenous prostaglandins can alter gastrin secretion. We have used primary cultures containing canine antral G-cells to study the cellular actions of prostaglandins on gastrin secretion, comparing the effects of prostaglandin E2 (PGE2) and its synthetic analogue enprostil. Enprostil (10(-10)-10(-6) M) inhibited gastrin secretion in response to bombesin, carbachol, and forskolin, the latter a receptor-independent activator of adenylate cyclase. This inhibition by enprostil was reversed by treatment with pertussis toxin (200 ng/ml, 8 h). However, enprostil did not inhibit the postreceptor stimuli 8-bromoadenosine 3',5'-cyclic monophosphate (10(-3) M), calcium ionophore A-23187 (10(-7) M), or 4 beta-phorbol 12-myristate 13-acetate (10(-8) M). In contrast, whereas PGE2 inhibited forskolin-stimulated gastrin release, PGE2 did not inhibit the response to carbachol or bombesin in control cultures. However, in pertussis toxin-treated cultures, PGE2 inhibition was reversed and, in contrast, the responses to bombesin, carbachol, and possibly forskolin were augmented. Indomethacin at a dose of 10(-5) M did not alter basal or bombesin-stimulated gastrin secretion. However, the somatostatin antibody CURE-S6 enhanced the response to forskolin and enhanced inhibition by PGE2, suggesting that endogenous somatostatin produced an inhibitory tone in these cultures and excluding the possibility that PGE2 acted via release of endogenous somatostatin. Our data suggest that in cultured antral cells gastrin release is regulated by inhibitory and stimulatory prostaglandin mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of prostaglandins on gastrin release from canine antral mucosal cells in primary culture. 814 Dec 91


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