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)

An in vivo preparation, in which a body plethysmograph was incorporated, was useful in monitoring the cardiopulmonary effects of pharmacological agents in the guinea pig and rabbit. Isoproterenol, given 30 seconds prior to histamine challenge, reproducibly blocked histamine-induced dynamic compliance decreases and increased heart in the artificially ventilated guinea pig. These effects were used to separate the activity of beta adrenergic blockers on airway and heart muscle. Dose-response data were obtained and ED50 values for pulmonary and cardiovascular blockade were compared. Relative potencies and cardioselectivity ratios for dichloroisoproterenol, practolol, dl-propranolol and d-propranolol were determined. Both practolol and dichloroisoproterenol were cardioselective; dl-propranolol was found to be the most potent. When a similar protocol was tried in the rabbit, isorpoterenol failed to antagonize either histamine or methacholine-induced airway constriction. This finding was supported in subsequent in vitro tests. Isoproterenol and epinephrine were ineffective in blocking methacholine-induced tracheal chain contractions and epinephrine did not significantly enhance adenylate cyclase activity. Our observations suggest rabbit airway smooth muscle is insensitive to beta adrenergic stimulants.
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PMID:Differences in pulmonary and cardiovascular beta receptors in the guinea pig and rabbit. 1 99

Some of the effects of beta-adrenergic agonists and antagonists on the adenylate cyclase system of human fat cell ghosts were studied. Isoproterenol, by causing about a fourfold increase of enzyme activity, was more potent than epinephrine and norepinephrine (about 2.5--3.0-fold stimulation). The beta2-adrenergic agonists salbutamol, terbutalin, and fenoterol were considerably less effective than the naturally occurring catecholamines. The stimulatory actions of isoproterenol and beta2-adrenergic agonists were competitively inhibited by the beta-blocking agent propranolol. Isoproterenol stimulation was also inhibited by the selective beta1-adrenergic antagonist practolol. This compound, however, was less potent than propranolol. The results are suggestive for an adenylate cyclase system in human fat cell ghosts coupled to beta1-adrenergic receptor sites. These receptors differ from the cardiac beta receptors with respect to practolol affinity.
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PMID:Catecholamine-sensitive adenylate cyclase of human fat cell ghosts: a comparative study using different beta-adrenergic agents. 2 May 50

Arachidonic acid-induced platelet aggregation was inhibited by prostaglandins E1 and F2alpha(PGE1 and PGF2alpha), papaverine and dibutyryl cycle AMP. Prostaglandin E2 displayed a biphasic effect, as concentrations below 2 muM potentiated aggregation, whereas concentrations above it were inhibitory. Isoproterenol (up to 10 mM) failed to block aggregation but inhibition was uncovered in presence of adrenergic alpha-blocking agents. Isoproterenol potentiated aggregation due to sub-threshold amounts of arachidonic acid, and this effect, but not that due to PGE2, was suppressed by the alpha-blocking agents. Isoproterenol and PGE2 appear thus to enhance arachidonic acid-induced platelet aggregation after interacting with different receptor sites. The yield of rabbit aorta contracting activity formed during AA-induced aggregation was markedly reduced by PGE1, dibutyryl cyclic AMP and high concentrations of PGE2, and was increased by low concentrations of the latter. PG-like activity was not significantly reduced when aggregation and generation of rabbit aorta contracting activity were inhibited by bibutyryl cyclic AMP. It is hypothesized that interaction of human platelets and arachidonic acid results in formation of different pharmacologically active materials, possibley bearing similar lipoperoxide structures. Generation of one portion of these materials is controlled by the adenyl cyclase-cyclic AMP system, whereas another portion, that comprises the natural PG, is cyclic AMP-independent. Prostaglandins formed during platelet aggregation have a regulatory role and modulate the platelet response, rather than constitute a trigger stimulus for aggregation.
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PMID:Substances that increase the cyclic AMP content prevent platelet aggregation and the concurrent release of pharmacologically active substances evoked by arachidonic acid. 5 79

1. Cyclic adenosine 3',5'-monophosphate and N-6-2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate decrease the initial entry rate and the steady-state uptake of p-aminohippurate and uric acid by rabbit kidney cortex slices. 2. N-6-2'-O-Dibutyryl adenosine 3'-5'-monophosphate inhibits the tubular transport of p-aminohippurate competitively. 3. Isoproterenol, known to increase cyclic nucleotide concentration of the cortical tubules by activation of adenyl cyclase, decreases p-aminohippurate transport. Antidiuretic hormone which is known to stimulate only medullary adenyl cyclase has no effect on p-amino-hippurate uptake by cortical slices. 4. Theophylline, which inhibits cyclic nucleotide phosphodiesterase and, therefore, enhances the cellular accumulation of endogenous cyclic nucleotide, depresses p-aminohippurate transport.
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PMID:Inhibition by cyclic AMP and dibutyryl cyclic AMP of transport of organic acids in kidney cortex. 16 97

Isoproterenol, a stimulator of adenylate cyclase, was used to select a stable variant clone of mouse lymphosarcoma cells deficient in the enzyme. The inability of four different stimulators to activate cyclic adenosine monophosphate synthesis in the variant, in contrast to its wild-type parent, implies that in normal cells one type of adenylate cyclase molecular can respond to different activators.
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PMID:Selection of a variant lymphoma cell deficient in adenylate cyclase. 16 87

Isoproterenol plus guanylyl imidodiphosphate (Gpp(NH)p) activate frog erythrocyte adenylate cyclase to a level much higher than the sum of the activities produced by the catecholamine and the synthetic nucleotide tested separately. Propranolol, the beta-receptor blocking agent, failed to inhibit activity when added after the enzyme system had been preincubated with both isoproterenol and Gpp(NH)p. However, if propranolol was added after only one of the two components had been added, it inhibited the effect of isoproterenol. Production of the propranolol-resistant state by treatment with isoproterenol and Gpp(NH)p did not require the presence of the productive substrate (MgATP). The activated propranolol-resistant state persisted following various treatments of the enzyme preparation including extensive washings of the membranes; considerable activity was retained even after sonication or treatment with the detergent Lubrol-PX, treatments which caused inactivation of the native enzyme. Extensive dilution of the membranes following pretreatment with isoproterenol and Gpp(NH)p did not significantly reduce to the activity of the enzyme. Readdition of isoproterenol after dilution caused some inhibition of adenylate cyclase activity, indicating apparently that the beta-receptor has not become inaccessible. In contrast, preincubation with isoproterenol alone failed to render the enzyme system refractive to propranolol, and dilution readily reduced the activity to negligibly low values. Preincubation with Gpp(NH)p alone also produced a persistent active state but the activity was much lower than that obtained throught the combined action of isoproterenol and Gpp(NH)p. The findings suggest that the hormone may be required only to facilitate the initial interaction of the enzyme with Gpp(NH)p. The differences, in this respect, between Gpp(NH)p and the more labile natural nucleotide, GTP, are discussed.
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PMID:A persistent active state of the adenylate cyclase system produced by the combined actions of isoproterenol and guanylyl imidodiphosphate in frog erythrocyte membranes. 16 23

The role of cyclic AMP in stimulus-secretion coupling with investigated in rat parotid tissue slices in vitro. Isoproterenol and norepinephrine stimulated a rapid intracellular accumulation of cyclic AMP, which reached a maximum level of 20-30 times the control value by 5 to 10 min after addition of the drug. Isoproterenol was approximately ten times more potent in stimulating both alpha-amylase release and cyclic AMP accumulation than were norepinephrine and epinephrine, which had nearly equal effects on these two parameters. Salbutamol and phenylephrine were less effectivema parallel order of potency and sensitivity was observed for the stimulation of adenylate cyclase activity in a washed particulate fractionmthe results suggest that these drugs are acting on a parotid acinar cell through a beta1-adrenergic mechanismmat the lowest concentrations tested, each of the adrenergic agonists stimulated significant alpha-anylase release with no detectable stimulation of cyclic AMP accumulationmeven in the presence of theophylline, phenylephrine at several concentrations increased alpha-amylase release without a detectable increase in cyclic AMP levels. However, phenylephrine did stimulate adenylate cyclase. These data suggest that, under certain conditions, large increases in the intra-cellular concentration of cyclic AMP may not be necessary for stimulation of alpha-amylase release by adrenergic agonists. Also consistent with this idea was the observation that stimulation of cyclic AMP accumulation by isoproterenol was much more sensitive to inhibition by propranolol than was the stimulation of alpha-amylase release by isoproterenol. Stimulation of alpha-amylase release by phenylephrine was only partially blocked by either alpha- or beta-adrenergic blocking agents, whereas stimulation of adenylate cyclase by phenylephrine was blocked by propranolol and not by phentolaminemphenoxybenzamine and phentolamine potentiated the effects of norepinephrine and isoproterenol on both cyclic AMP accumulation and alpha-amylase release by N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate; These observations may indicate a non-specific action of phenoxybenzamine, and demonstrate the need for caution in interpreting evidence obtained using alpha-adrenergic blocking agents as tools for investigation of alpha- and beta-adrenergic antagonism.
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PMID:Effect of adrenergic agents on alpha-amylase release and adenosine 3',5'-monophosphate accumulation in rat parotid tissue slices. 16 57

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. 17 62

Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E1 (PGE1) and GTP. Isoproterenol activation was additive with PGE1, as was that of secretin with PGE1, but only in the presence of GTP. Secretin activation in the presence of PGE1 and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE1 and guanine nucleotide modulation of the adenyl cyclase activation process.
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PMID:Hormonal regulation of pancreatic islet adenyl cyclase. 17 51

Hydroxyurea was used to study the proliferation rate of haemopoietic stem cells (CFUs) in normal mice, after irradiation or transplantation into irradiated recipients. It was demonstrated that the proliferation rated of endogenous CFUs (endo-CFUs) and exogenous CFUs (exo-CFUs) are identical. After irradiation (650 R) the surviving endo-CFUs begin to proliferate immediately. By contrast exo-CFUs transplanted into the irradiated recipient mouse (850 R), begin to proliferate only after about 30 hr. However, injection of isoproterenol (which stimulates adenyl cyclase) or dibutyryl cyclic adenosin 3',5'-monophosphate shortly after marrow cell graft, triggers the transplanted CFUs into cell cycle as shown by an almost immediately increased sensitivity to hydroxyurea. Isoproterenol is capable of inducing DNA synthesis also in stem cells of normal mice but it takes about 20 hr before CFUs become to be increasingly sensitive to hydroxyurea.
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PMID:Study on the proliferative state of haemopoietic stem cells (CFU). 17 46


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