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 type of catecholamine receptor involved in the regulation of serotonin N-acetyltransferase (NAT) activity and melatonin (N-acetyl-5-methoxytryptamine) level in chicken retina was compared to that regulating these parameters in the pineal gland. Systemic administration of apomorphine, a dopamine receptor agonist, resulted in marked inhibition of the nocturnal increase of retinal NAT activity and melatonin content. Apomorphine did not affect NAT activity or melatonin content of the pineal gland. In contrast, clonidine, an alpha-2 adrenergic receptor agonist, inhibited the nocturnal rise in pineal NAT activity and melatonin content although being without effect on these parameters in retina. Apomorphine-induced inhibition of retinal NAT activity was blocked by spiperone, a D2-dopamine receptor antagonist, but not by antagonists of D1-dopamine, alpha-1, alpha-2 and beta adrenergic receptors. Systemic or intraocular injection of quinpirole, a D2-dopamine receptor agonist, in the middle of the dark phase of the light-dark cycle markedly reduced retinal NAT activity and melatonin level, whereas injections of SKF 38393-A, a D1-dopaminergic agonist, had no effect. The inhibitory effect of clonidine on pineal NAT activity was blocked by yohimbine, an alpha-2 adrenergic receptor antagonist. The results presented in this paper demonstrate that NAT activity and melatonin content in chicken retina and pineal gland are differentially modulated in vivo by D2-dopamine and alpha-2 adrenergic receptors, respectively. Despite the different types of receptors involved, both tissues may share a common pathway for catecholamine-mediated inhibition of melatonin biosynthesis, i.e., inhibition of adenylate cyclase activity.
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PMID:Catecholamine receptors regulating serotonin N-acetyltransferase activity and melatonin content of chicken retina and pineal gland: D2-dopamine receptors in retina and alpha-2 adrenergic receptors in pineal gland. 256 81

The characteristics and localization of beta adrenoceptor subtypes in rat kidney sections have been examined using [125I]cyanopindolol and in vitro labeling combined with autoradiography. Binding was stereoselective since the (-)-isomers of propranolol and pindolol were some two orders of magnitude more effective as competitors than the (+)-isomers. Competition curves obtained using the subtype selective antagonists ICI 118,551 (beta-2) and betaxolol (beta-1) had low pseudo Hill coefficients and were resolved into two distinct components representing beta-1 (63%) and beta-2 adrenoceptors (37%). Combined autoradiographic and histochemical studies using nuclear emulsion-coated coverslips and alkaline phosphatase staining showed that the majority of receptors were in the renal cortex and in the outer band of the medulla with fewer receptors associated with the inner medulla, papilla and renal blood vessels. Delineation of beta-1 and beta-2 adrenoceptor subtypes with the selective antagonists betaxolol and ICI 118,551 indicated that the highly localized receptors were predominately of the beta-1 subtype, associated with glomeruli and with tubules that from their staining characteristics and topography represent distal and cortical collecting tubules with few if any receptors associated with proximal tubules. Beta-2 adrenoceptors were more diffusely distributed in the cortex and there were minor areas of localization in the inner medulla. Although some glomerular beta adrenoceptors probably play a role in control of renin release, their distribution throughout this structure indicates that they also control other functions. The distribution of beta adrenoceptors in tubules corresponds well with the known distribution of beta adrenoceptor-stimulated adenylate cyclase in rat kidney and indicates that these receptors subserve a physiological function.
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PMID:Localization of beta adrenoceptor subtypes in rat kidney by light microscopic autoradiography. 298 17

A model for the regulation of erythropoietin production has been presented. This model proposes that a primary O2-sensing reaction in the kidney is initiated by a decrease in ambient PO2, a rapid decrease in gas exchange in the lung, a diminished oxygen-carrying capacity of hemoglobin, a molecular deprivation of oxygen, or a decrease in renal blood flow. It is proposed that the primary oxygen-sensing reaction may trigger the release of several mediators that stimulate adenylate cyclase through a receptor-activated stimulation of a G protein in the renal cell membrane. Some of the agents that are thought to be released during hypoxia, which may trigger this cascade, are adenosine (A2 activation), eicosanoids (PGE2, PGI2, and 6-keto PGE1), oxygen-free radicals (superoxide and H2O2), and catecholamines with beta-2 adrenergic receptor agonist properties. The activation of adenylate cyclase generates cyclic AMP, which activates protein kinase A, leading to the production of a phosphoprotein that, in turn, activates a nuclear protein involved in transcription and/or translation for erythropoietin biosynthesis and/or secretion. A second part of this model concerns the effect of hypoxia on a renal cell membrane phosphodiesterase and the generation of inositol triphosphate and diacylglycerol. Diacylglycerol may interact with diacylglycerol lipase to generate arachidonic acid, which, together with arachidonic acid generated by the interaction of phospholipase A2 on membrane phospholipids, produces eicosanoids. Eicosanoids may play a secondary role in Ep production/secretion. The model further proposes that calcium levels in both renal and liver cells may be important in regulating erythropoietin biosynthesis and/or secretion. It is proposed that an increase in intracellular calcium leads to the inhibition of erythropoietin biosynthesis and/or secretion and a decrease in intracellular calcium increases erythropoietin production. The specific mechanism by which calcium regulates erythropoietin biosynthesis and secretion is not well understood. However, a good correlation is seen with several agents that decrease intracellular calcium and increase erythropoietin production as well as with other agents that increase intracellular calcium and decrease erythropoietin production. When inositol triphosphate levels are increased, an increase in the mobilization of intracellular calcium from the endoplasmic reticulum or another intracellular pool occurs. This increased intracellular calcium probably activates a calcium calmodulin kinase and produces a phosphoprotein that inhibits erythropoietin production/secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacologic modulation of erythropoietin production. 328 82

Effects of ethanol (EtOH) on the alpha 2-receptor-coupled adenylate cyclase (AC) of the human platelet were examined. EtOH increased "basal" AC activity in a linear dose dependent manner. In the presence of Gpp(NH)p (2.5 microM), however, the slope of the dose-response curve for EtOH stimulation of AC activity was biphasic. The increase in activity produced by the addition of EtOH concentration between 0 and 100 mM was much sharper than the increase in activity produced by the concentration in excess of 100 mM. EtOH increased the rate of activation of AC by guanine nucleotides and concomitantly decreased the concentration of magnesium required for half-maximal activation of AC. Prostaglandin-E1 (PGE1) alone stimulated AC activity. Clonidine (3 nM-1 microM) diminished the PGE1 (1 microM)-stimulated AC by a maximum of 30%. EtOH did not alter the concentration of clonidine required for half-maximal inhibition of AC. Our results suggest that the sites of EtOH's action can be assigned to the direct action of the catalytic subunit and to the Ns-protein. Our results also indicate a substantial difference in EtOH's action on catecholamine receptor systems coupled in a stimulatory versus inhibitory manner to AC. Stimulation of AC through Ns-protein is potentiated by EtOH, but inhibition of AC through the Ni-protein is little affected by EtOH.
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PMID:Effects of ethanol on adenylate cyclase system in the human platelet. 342 58

Long-term regulation of the cyclic nucleotide phosphodiesterase of the C-6 rat glioma cell line has been studied. Both the low K(m) and high K(m) activities can be induced by elevation of intracellular cyclic AMP levels following either dibutyryl cyclic AMP or norepinephrine treatment of the cells. The enzymes are maximally induced by 3-4 hr. The presence of either cycloheximide or actinomycin D prevents induction by either dibutyryl cyclic AMP or norepinephrine. Evidence is presented that the norepinephrine effect is mediated by the beta-catecholamine receptor. The increased phosphodiesterase activity causes a partial refractoriness to a second challenge with norepinephrine, which can be overcome by blockade of the induction with cycloheximide. The results suggest that just as short-term regulation of cyclic AMP levels occurs via changes in the rates of synthesis or degradation, long-term alterations of the system may also involve either the adenylate cyclase or the phosphodiesterase.
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PMID:Cyclic AMP-mediated induction of the cyclic AMP phosphodiesterase of C-6 glioma cells. 415 39

Turkey erythrocyte membranes showed specific binding of [(3)H]epinephrine. The concentration of hormone required for half-maximal binding (30 muM) was the same as that required for half-maximal activation of the adenylate cyclase located in the same membrane preparation. The binding reaction at 37 degrees C reached completion during the first minute of incubation, which agrees well with the known rapidity of the biological response to catecholamines. Specific binding was abolished by heating the membranes 1 min at 100 degrees C. Chromatography of the bound (3)H, after its extraction from the membranes, indicated that the hormone had fully retained its chemical structure. Epinephrine binding was inhibited by the beta-adrenergic blocking agent propranolol, which also inhibited the activation of adenylate cyclase by the hormone. The specificity of phenethylamine derivatives in displacing [(3)H]epinephrine from the binding sites showed that a typical catecholamine receptor was responsible for the binding. Displacement of the bound hormone by analogs lacking the catechol group was more extensive at 37 degrees C than at 0 degrees C. Some of the analogs that displaced epinephrine from the binding site caused only a feeble activation of the adenylate cyclase, but were able to inhibit the activation of the enzyme by epinephrine. Thus, binding to a catecholamine receptor on a membrane preparation is an essential, but insufficient, condition to elicit a response.
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PMID:Epinephrine binding to the catecholamine receptor and activation of the adenylate cyclase in erythrocyte membranes (hormone receptor- -adrenergic receptor-cyclic AMP-turkey). 450 Nov 30

5'-Guanylylimidodiphosphate (Gpp(NH)-p) stimulates adenylate cyclase [ATP-pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in plasma membranes isolated from frog and salmon erythrocytes, from rat adrenal, hepatic, and fat cells, and from bovine thyroid cells. The nucleotide acts cooperatively with the various hormones (glucagon, secretin, ACTH, thyrotropin, and catecholamines) that stimulate these adenylate cyclase systems with resultant activities that equal or exceed those obtained with hormone plus GTP or with fluoride ion. In the absence of hormones, Gpp(NH)p is a considerably more effective activator than GTP, and, under certain conditions of incubation, stimulates rat fat cell adenylate cyclase to levels of activity (about 20 nmoles of 3',5'-adenosine monophosphate mg protein per min) far higher than reported hitherto for any adenylate cyclase system examined. The nucleotide activates frog erythrocyte adenylate cyclase when the catecholamine receptor is blocked by the competitive antagonist, propranolol, and activates the enzyme from an adrenal tumor cell line which lacks functional ACTH receptors. In contrast, Gpp(NH)p does not stimulate adenylate cyclase in extracts from Escherichia coli B. Gpp(NH)p appears to be a useful probe for investigating the mechanism of hormone and nucleotide action on adenylate cyclase systems in eukaryotic cells.
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PMID:5'-Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells. 460 68

Primary cultures of bovine adrenal medullary chromaffin cells were used to study the regulation of opioid peptide (OP) synthesis. Chromaffin cells continuously exposed to tetrabenazine, a drug that depletes cellular catecholamine stores, increase their OP contents between 32 hr and 6 days of treatment. At no time following tetrabenazine addition were increases in opiate receptor-inactive enkephalin-containing peptides (IECPs) observed. Because IECPs may serve as precursors to OPs, these results suggest increased processing of OP precursors following treatment with catecholamine-depleting drugs in addition to an increased rate of OP precursor synthesis. The increases in cellular OP levels induced by tetrabenazine were approximately proportional to the depletion in cellular catecholamines produced by this drug. Also, the effects of tetrabenazine on chromaffin cell OP and IECP contents were mimicked by inhibitors of catecholamine biosynthesis and other agents that decreased catecholamine stores, but not by supplementing the culture medium with catecholamines or catecholamine receptor agonists. Addition of 8-bromo-cAMP or forskolin, an activator of adenylate cyclase, to chromaffin cell cultures increased both OP and IECP stores. Inhibitors of cyclic nucleotide phosphodiesterase also increase chromaffin cell OP and IECP contents, although it is unclear whether these increases result from increased cyclic nucleotide levels. Hence, both alterations in some intracellular catecholamine pool and elevations of cAMP levels may trigger increases in the synthesis and processing of OPs and IECPs in the adrenal medullary chromaffin cell.
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PMID:Regulation of opioid peptide synthesis and processing in adrenal chromaffin cells by catecholamines and cyclic adenosine 3':5'-monophosphate. 609 47

The effects of a nonselective (isoproterenol), a beta-1 selective (prenalterol) and a beta-2-selective (procaterol) agonist on beta adrenoceptor occupancy, adenylate cyclase activity and muscle contractions in the myocardium (beta-1) and soleus muscle (beta-2) of the reserpine-pretreated cat were investigated. Each compound fully inhibited the specific binding of [125I] iodohydroxybenzylpindolol in both tissues. Myocardial and soleus muscle adenylate cyclase were equipotently activated by isoproterenol. Prenalterol and procaterol induced no more than marginal elevations in myocardial enzyme activity and only the latter compound produced an increase in soleus muscle adenylate cyclase activity (77% of that produced by isoproterenol). Prenalterol increased myocardial contractility (82% of that of isoproterenol) in a monophasic concentration-dependent manner, as did isoproterenol, whereas procaterol induced a biphasic inotropic response. The high affinity effect (23% of isoproterenol) of procaterol was selectively blocked by IPS 339 (beta-2-selective) and the low affinity component (70% of isoproterenol) was blocked by pamatolol (beta-1-selective). Isoproterenol and procaterol decreased subtetanic soleus muscle contractions equally, whereas prenalterol was devoid of effect in skeletal muscle. From the interrelations between the concentration-effect curves for these drug-induced responses, it was estimated that under the conditions used in these assays a full agonist in the heart has a spare beta-1 adrenoceptor pool of 80 to 90%. A corresponding beta-2 adrenoceptor reserve of 30 to 50% was derived from data obtained in the soleus muscle. On the basis of the present data, prenalterol may be characterized as a nonselective beta adrenoceptor ligand with beta-1 adrenoceptor partial agonistic activity.
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PMID:Beta adrenoceptor interaction of full and partial agonists in the cat heart and soleus muscle. 611 57

In the preceding paper, we described the parallel effect of amphipathic drugs on the fluidity and adenylate cyclase activity of pigeon erythrocyte membrane. This parallelism was found when the cyclase activity was assayed in the presence of a guanyl nucleotide and with Mg-ATP as the substrate after a preincubation of the membrane with the drugs [Salesse, R., Garnier, J., Leterrier, F., Daveloose, D., & Viret, J. (1982) Biochemistry (preceding paper in this tissue)]. However, when the regulatory protein (N) and the catalytic unit (E) were precoupled by GppNHp or fluoride before the action of the drugs, the cyclic AMP production was never inhibited. Thus, the drug-induced fluidization appeared to interfere with the efficiency of the activating coupling between N and E. Chlorpromazine even enhanced the cyclase activity: if the catecholamine receptor (R) repressed the cyclase activity in the absence of hormone [Rodbell, M. (1980) Nature (London) 284, 17-22], the loss of R molecules with chlorpromazine would prevent this inhibition and lead to hyperactivity of the enzyme. On the other hand, the comparison between two states of the adenylate cyclase system, (1) N and E reversibly precoupled in the presence of GTP and (2) R, N, and E precoupled in the presence of GTP plus isoproterenol, showed no difference between the activity curves at various drug concentrations: this may be interpreted as a permanent coupling of R and N. The main control exerted by fluidity on the activity of the adenylate cyclase system would thus be at the level of the activating coupling between the N subunit and the catalytic unit in pigeon erythrocyte membrane.
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PMID:Modulation of adenylate cyclase activity by the physical state of pigeon erythrocyte membrane. 2. Fluidity-controlled coupling between the subunits of the adenylate cyclase system. 628 9


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