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 effects of cholera toxin on mucosal cyclic nucleotide concentrations and on net fluid secretion in the porcine small intestine are reported. Cholera toxin causes net secretion of fluid into the small intestine of weanling pigs, and secretory rates are dependent on the dose of the toxin placed in intestinal loops. Intestinal secretion due to cholera toxin exposure was not consistently accompanied by elevated concentrations of mucosal cyclic AMP or cyclic GMP. Net fluid fluxes in individual loops did not correlate with mucosal cyclic AMP concentration in the same loop. Jejunal adenylate cyclase was activated to a lesser extent in pigs, compared with rabbits, after in vivo treatment with cholera toxin. In vitro activation in cell-free homogenates was similar for both species. Papaverine was similar to cholera toxin in causing fluid secretion without cyclic AMP accumulations, but 3-isobutyl-1-methyl xanthine significantly increased cyclic AMP concentration and induced fluid secretion in pigs. Weanling pigs appeared to differ from rabbits in having a secretory response to cholera toxin which was independent of elevations in total mucosal cyclic AMP concentration.
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PMID:Cholera toxin effects on fluid secretion, adenylate cyclase, and cyclic AMP in porcine small intestine. 8 Mar 78

Quantitative studies of the action of theophylline and papaverine were performed in rat epididymal fat pads, both on the lipolytic effect and on the activity of phosphodiesterase, adenylate cyclase and protein kinase. Papaverine, a stronger inhibitor of phosphodiesterase than theophylline, did not produce lipolysis. The maximum lipolytic effect (glycerol release) of theophylline was much higher than that of epinephrine and nearly approached the effect exerted by dibutyryl cyclic AMP. While theophylline potentiated or was without any effect on lipolysis produced by epinephrine and dibutyryl cyclic AMP, papaverine at concentration 10- minus 3 M reduced the effect of both drugs as well as of theophylline by 90 per cent. These concentrations of papaverine also strongly inhibited the activity of adenylate cyclase. Neither papaverine nor theophylline prevented the activation of protein kinase by cyclic AMP. The data suggest that the lack of a lipolytic effect of papaverine migth be caused by a combination of its inhibitory effect on adenylate cyclase and direct inhibition of activation of triglyceride lipase.
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PMID:The absence of stimulation of lipolysis by papaverine, a strong inhibitor of phosphodiesterase. 16 81

The effect of five phosphodiesterase (PDE) inhibitors (papaverine, IBMX, theophyllamine, dipyridamol and M & B 22,948) was studied on adenylate cyclase and on cyclic nucleotide phosphodiesterase activities in extracts of rat caudate nucleus. For comparison the effect on DA turnover and on turning behaviour in rats with unilateral lesions of the nigro-neostriatal DA nerurons was studied. Cyclic AMP PDE was inhibited by papaverine, dipyridamol, IBMX, M & B 22,948 and theophyllamine in that order of potency. Cylcic GMP PDE was inhibited by IBMX, papaverine, M & B 22,948 and theophyllamine, but not by dipyridamol. Basal adenylate cyclase washigher if assayed in the presence of papaverine or dipyridamol than if theophyllamine or IBMX was present. The degree of stimulation caused by DA was not significantly influenced by the PDE inhibitors. Papaverine and dipyridamol enhanced DA disappearance in the caudate nucleus and the tuberculum accumbens, but not in the median eminence. Caffeine had no significant effect. Papaverine (1-28 mg/kg) had no signigicant effect on L-dopa (5 mg/kg)-induced turning, and actually inhibited turning induced by the combination of L-dopa (10 mg/kg) and atropine (5 mg/kg). The other four PDE inhibitors all potentiated L-dopa-induced turning. Theophyllamine (20 mg/kg) and IBMX (5 mg/kg) even caused turning when given alone. The data are compatible with the opinion that PDE inhibition leads to an enhanced effect of DA in the caudate nucleus. However, the results also demonstrate that several of the PDE inhibitors have effects on central DA mechanisms that are difficult to explain solely on the basis of PED inhibition.
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PMID:Effect of some phosphodiesterase inhibitors on central dopamine mechanisms. 18 7

Effects were examined of atropine, diazepam, pethidene, promethazine, scopolamine, omnopon and papaverine on basal and noradrenaline-stimulated lipolysis in rat isolated fat cells and on rat adipose tissue cyclic AMP phosphodiesterase activity. Papaverine at high concentration (1 mM) inhibited both basal and hormone-stimulated lipolysis, whereas diazepam enhanced basal lipolysis. At a 'clinical dose', omnopon increased both basal and noradrenaline-stimulated lipolysis. Adipose tissue cAMP phosphodiesterase activity was strongly inhibited by 1 mM diazepam, papaverine, promethazine and omnopon (280 microgram ml-1). Lack of enhancement of lipolysis by the established cAMP phosphodiesterase antagonist papaverine, is compatible with simultaneous inhibition also of adipose adenyl cyclase. Diazepam-stimulated lipolysis is compatible with its phosphodiesterase inhibitory activity. It is proposed that papaverine-containing omnopon may offer some survival advantages during surgical stress by facilitating a caloric supply.
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PMID:Effects of several preoperative medications on fat cell lipolysis, and activity of adipose tissue cyclic AMP phosphodiesterase. 22 65

Papaverine and theophylline both increase the chronotropic response of isolated rabbit atria, however, the maximum stimulation following papaverine is much smaller than that obtained with theophylline. When these phosphodiesterase inhibitors are used in conjunction with histamine (H1 and H2 receptor agonist), 2-(2-aminoethyl) pyrazole (H2 agonist) and 3-(2-aminoethyl) triazole (H1 agonist) the responses are all considerably more than additive. This suggests that both H1 and H2 histamine receptors can activate adenyl cyclase and therefore increase the formation of cyclic AMP in spite of reports that only H2 receptors stimulate adenyl cyclase.
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PMID:A comparison of the augmentation of H1 and H2 receptor agonist stimulation of rabbit atrial chronotropic response by two phosphodiesterase inhibitors, papaverine and theophylline. 69 24

CI-914 is a novel positive inotropic agent whose cardiotonic activity is not due to inhibition of Na+, K+-ATPase or to stimulation of cardiac beta-receptors. CI-914 also has no direct effect on sarcoplasmic reticulum, mitochondria or adenylate cyclase activity. CI-914 does, however, exert a potent inhibitory effect on cardiac phosphodiesterase activity. In evaluating the effect of this agent on the different molecular forms of phosphodiesterase present in cardiac muscle, CI-914 was found to selectively inhibit PDE III, which is a low Km, cAMP-specific form of the enzyme (IC50 = 6.1 microM). This inhibitory effect was found to be competitive with respect to the substrate. Papaverine and theophylline on the other hand were found to inhibit all three forms of phosphodiesterase present in cardiac muscle. The role of phosphodiesterase inhibition in mediating the positive inotropic response to CI-914 is supported by the finding that this agent: (i) significantly elevates cyclic AMP levels in ventricular tissue; (ii) shifts the normal concentration-response to the beta-receptor stimulant isoproterenol to the left: and (iii) restores contractility to K+-depolarized papillary muscles.
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PMID:Studies aimed at elucidating the mechanism of action of CI-914, a new cardiotonic agent. 300 93

Nucleoside diphosphokinase (NDK) of human platelets has been purified by chromatography on Blue Sepharose CL-6B gel (purification factor of 950) and shown to be free of adenylate kinase, ATPase and adenylate cyclase. The molecular weight was 70,000 with subunits of 17,000. The pH optimum was 8.0 Km values for ATP and dTDP were determined in two ways using the pyruvate kinase-lactate dehydrogenase coupled enzyme assay. Values of 0.38 and 0.20 mM were obtained for ATP and 0.29 and 0.21 mM for dTDP. Km values for ADP (0.024 mM) and GTP (0.12 mM) were determined with the hexokinase-glucose-6-phosphate dehydrogenase coupled enzyme assay. These values are in agreement with those reported for NDK from other sources. Theophylline, which inhibits the NDK activity of intact platelets and platelet membrane preparations and inhibits the ADP-induced shape change of platelets, was shown to be a competitive inhibitor of both the free and phosphorylated forms of NDK with competitive inhibition constants (Kic) of 9.3 and 9.6 mM respectively. Papaverine, another cAMP phosphodiesterase inhibitor, which also inhibits the ADP-induced shape change of platelets, had no inhibitory effect on platelet NDK. It was concluded that the inhibitory effect of theophylline on the activity of the purified enzyme was due to the structural similarity between the methylxanthine and the adenine moiety of ADP.
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PMID:Isolation and kinetic studies of nucleoside diphosphokinase from human platelets and effects of cAMP phosphodiesterase inhibitors. 302 50

The effects of forskolin analogs, phosphodiesterase inhibitors and 8-bromo cyclic AMP on plasma exudations induced with bradykinin and prostaglandin E1 in rat skin were investigated using [125I]bovine serum albumin (125I-BSA). Forskolin, forskolin 7-ethyl carbonate and 7-desacetylforskolin, which are potent activators of adenylate cyclase, greatly potentiated the bradykinin-induced plasma exudation and inhibited the prostaglandin E1-induced response. On the other hand, 14,15-dihydroforskolin and 1,9-dideoxyforskolin, which are weak or inactive as activators of adenylate cyclase, did not have any significant effect on bradykinin and prostaglandin E1-induced plasma exudations. The phosphodiesterase inhibitors, ZK 62711, dipyridamole, HL 725, and 3-isobutyl-1-methylxanthine potentiated the bradykinin-induced plasma exudation and inhibited the prostaglandin E1-induced response. Papaverine had biphasic effects on the bradykinin-response and slight inhibitory effects on the prostaglandin E1-response. 8-Bromo cyclic AMP in the doses of 0.01 to 1 microgram potentiated the bradykinin-induced plasma exudation, but had no effect at doses of 10 and 100 micrograms. 8-Bromo cyclic AMP at all doses significantly inhibited the prostaglandin E1-induced response. The results suggest that the effects of forskolin and its analogs on plasma exudations induced with bradykinin and prostaglandin E1 in rat skin derive from activation of cyclic AMP-generating systems.
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PMID:Effects of forskolin analogs, phosphodiesterase inhibitors and 8-bromo cyclic AMP on plasma exudations induced with bradykinin and prostaglandin E1 in rat skin. 631 36

Recent in vivo and in vitro studies suggest that nitric oxide or a nitric-oxide-like substance mediates nonadrenergic, noncholinergic relaxation of trabecular smooth muscle through activation of the cyclic guanosine monophosphate (cGMP) pathway. In 60 Sprague-Dawley rats, we investigated the effect of intracavernous administration of different drugs known to act at different levels of the cyclic adenosine monophosphate (cAMP) and cGMP pathways. Neither cAMP nor drugs that stimulate adenylate cyclase activity (vasoactive intestinal peptide, prostaglandin E1, calcitonin gene-related peptide) provoked any change in the basal intracavernous pressure. N-ethylmaleimide, an inhibitor of the enzyme adenylate cyclase, did not modify the response to electrostimulation of the cavernous nerve, indicating that the cAMP pathway does not play a significant role in penile erection in rats. However, intracavernous administration of methylene blue, a guanylate cyclase inhibitor, significantly reduced the response to electrostimulation (p = 0.001). Direct intracavernous injection of cGMP caused a statistically significant, dose-dependent increase in intravenous pressure that was not significantly inhibited by methylene blue. Sodium nitroprusside, a nitric oxide releaser and therefore a guanylate cyclase activator, caused a dose-dependent increase in intracavernous pressure (p < 0.05) that was inhibited almost completely by methylene blue (p = 0.002), supporting the theory that nitric oxide activates the synthesis of cGMP and that cGMP causes cavernous smooth muscle relaxation. Papaverine elicited an intracavernous pressure increase that was not affected by methylene blue or N-ethylmaleimide, indicating that papaverine acts through an independent pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic guanosine monophosphate mediates penile erection in the rat. 790 62

The effect of dopamine on the arterioles (50.8-95.2 microns) in the cremaster muscle was examined to determine its effect on microcirculation. Anesthetized rats were used under a light microscope connected to a videocamera. Drugs were applied using small round filter paper (370 microns in diameter) containing the drug and placed in the immediate vicinity of the arteriole on the cremaster with a micromanipulator. The dose of the drug applied was represented by concentration of the drug solution in which the filter paper was immersed. Dopamine (10(-6)-10(-4)M) induced neither constriction nor dilation of the arteriole in the cremaster. Papaverine (10(-2)M) did not dilate the arteriole. However, the arterioles were constricted by noradrenaline (10(-6)-10(-4)M) and vasopressin (10(-7)M) in a dose-dependent manner. Noradrenaline (10(-4)M)-induced constriction was blocked by concomitant application of dopamine (10(-4)M). This effect of dopamine was antagonized by SCH23390 (10(-3)M). However, isoproterenol (10(-3)M) did not affect the arteriole, nor inhibit noradrenaline (10(-4)M)-induced constriction of the arterioles. While forskolin (10(-2)M) alone did not produce constriction or dilation of the arterioles, it inhibited noradrenaline (10(-4)M)-induced constriction of the arteriole. These results suggest that dopamine prevents the constriction of the arteriole induced by noradrenaline, by activation of DA1 receptors, which activates adenylate cyclase.
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PMID:Inhibitory effects of dopamine on noradrenaline-induced constriction of arterioles in vivo in the striated cremaster muscle. 848 19


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