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)

1. Renal tubular membranes from rat kidneys were prepared, and adenylate cyclase activity was measured under basal conditions, after stimulation by NaF or salmon calcitonin. Apparent Km value of the enzyme for hormone-linked receptor was close to 1 x 10(-8) M. 2. The system was sensitive to temperature and pH. pH was found to act both on affinity for salmon calcitonin-linked receptor and maximum stimulation, suggesting an effect of pH on hormone-receptor binding and on a subsequent step. 3. KCl was without effect areas whereas CoCl and CaCl2 above 100 muM and MnCl2 above 1 muM inhibited F- -and salmon calcitonin-sensitive adenylate cyclase activities. The Ca2+ inhibition of the response reflected a fall in maximum stimulation and not a loss of affinity of salmon calcitonin-linked receptor for the enzyme. 4. The measurement of salmon calcitonin-sensitive adenylate cyclase activity as a function of ATP concentration showed that the hormone increases the maximum velocity of the adenylate cyclase. GTP, ITP and XTP at 200 muM did not modify basal, salmon calcitonin- and parathyroid hormone-sensitive adenylate cyclase activities. 5. Basal, salmon calcitonin- and F- -sensitive adenylate cyclase activities decreased at Mg2+ concentrations below 10 mM. High concentrations of Mg2+ (100 mM) led to an inhibition of the F- -stimulated enzyme. 6. Salmon calcitonin-linked receptor had a greater affinity for adenylate cyclase than human or porcine calcitonin-linked receptors. There was no additive effect of these three calcitonin peptides whereas parathyroid hormone added to salmon calcitonin increased adenylate cyclase activity, thus showing that both hormones bound to different membrane receptors. Human calcitonin fragments had no effect on adenylate cyclase activity. 7. Salmon calcitonin-stimulated adenylate cyclase activity decreased with the preincubation time. This was due to progressive degradation of the hormone and not to the rate of binding to membrane receptors.
Biochem J 1975 Sep
PMID:Calcitonin-sensitive adenylate cyclase in rat renal tubular membranes. 0 53

Catecholamines substituted to agarose were synthesized in various ways. Norepinephrine and isoproterenol were linked to p-aminobenzamidohexyl agarose by an azo linkage to the catechol ring. Norepinephrine was also couple to hexyl agaros via the amino group, forming an amino, guanidino or amido bond. Biological activity of the immobilized catecholamines was determined by assessing their abilities to interact with adenylate cyclase in several membrane preparations and intact preparations of erythrocytes. In dog heart membranes, stimulation of adenylate cyclase by the catecholamine-gels could be accounted for by leached hormone which had been released from the gels. In frog erythrocyte membranes, leaching was minimal and no significant stimulation of adenylate cyclase was observed. Agarose-immobilized catecholamines, however, competitively inhibited isoproterenol stimulation of adenylate cyclase in these erythrocyte membranes indicating that catecholamines which are bound to agarose interact with the beta-adrenergic receptors as antagonists rather than agonists. When tested on intact frog erythrocytes, agarose immobilzed catecholamines did not increase the intracellular levels of cyclic AMP, although isoproterenol caused as 8-10 fold rise in these levels. Similarly, when tested for antagonist activity in the intact cells the agarose-catecholamines failed to inhibit the stimulation of cyclic AMP caused by isoproterenol. The difference observed in the beta-adrenergic antagonist activity of the agarose-bound catecholamines in membrane preparations and intact cells can be attributed to steric factors which could have prevented the access of the bead-bound ligands with the surface of the cell or to the possibility that receptors might be buried in the membrane matrix.
Biochim Biophys Acta 1976 Sep 24
PMID:Biological activity of agarose-immobilized catecholamines. 0 46

Adenylate, guanylate cyclase and protein kinases in a fibrous sarcoma originating from rat prostate have been studied. A decrease in levels of adenosine 3', 5'-monophosphate (cyclic AMP) and adenylate cyclase activities and an increase in levels of guanosine 3',5'-monophosphate (cyclic GMP) and guanylate cyclase activities were observed in the tumor tissue when compared with the normal prostatic tissue of rats. Protein kinases from the tumor and the prostate were both responsive to exogenous cyclic AMP, with an apparent Ka of 0.08 muM in the tumor and of 0.11 muM in the prostate. It is of interest that the protein kinases from the tumor responded to cyclic AMP to the same extent as was observed in the enzyme preparation from the prostate. The protein kinase from the tumor was more sensitive to cyclic GMP than that from the prostate, showing an apparent Ka of 0.88 muM in the tumor and of 4.85 muM in the prostate. This tumor has been characterized with an increase in guanylate cyclase activities with a subsequent rise in cellular cyclic GMP and an increased sensitivity of the protein kinase to cyclic GMP.
Biochim Biophys Acta 1976 Sep 24
PMID:Studies on cyclic nucleotides in cancer. I. Adenylate guanylate cyclase and protein kinases in the prostatic sarcoma tissue. 0 48

The activities of adenylate and guanylate cyclase and cyclic nucleotide 3':5'-phosphodiesterase were determined during the aggregation of human blood platelets with thrombin, ADP, arachidonic acid and epinephrine. The activity of guanylate cyclase is altered to a much larger degree than adenylate cyclase, while cyclic nucleotide phosphodiesterease activity remains unchanged. During the early phases of thrombin-and ADP-induced platelet aggregation a marked activation of the guanylate cyclase occurs whereas aggregation induced by arachidonic acid or epinephrine results in a rapid diminution of this activity. In all four cases, the adenylate cyclase activity is only slightly decreased when examined under identical conditions. Platelet aggregation induced by a wide variety of aggregating agents including collagen and platelet isoantibodies results in the "release" of only small amounts (1-3%) of guanylate cyclase and cyclic nucleotide phosphodiesterase and no adenylate cyclase. The guanylate cyclase and cyclic nucleotide phosphodiesterase activities are associated almost entirely with the soluble cytoplasmic fraction of the platelet, while the adenylate cyclase if found exclusively in a membrane bound form. ADP and epinephrine moderately inhibit guanylate and adenylate cyclase in subcellular preparations, while arachidonic and other unsaturated fatty acids moderately stimulate (2-4-fold) the former. It is concluded that (1) the activity of platelet guanylate cyclase during aggregation depends on the nature and mode of action of the inducing agent, (2) the activity of the membrnae adenylate cyclase during aggregation is independent of the aggregating agent and is associated with a reduction of activity and (3) cyclic nucleotide phosphodiesterase remains unchanged during the process of platelet aggregation and release. Furthermore, these observations suggest a role for unsaturated fatty acids in the control of intracellular cyclic GMP levels.
Biochim Biophys Acta 1976 Sep 24
PMID:Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes. 0 49

Patients with atopic dermatitis have abnormal autonomic responses of the arterioles, pilomotor smooth muscle, and sweat glands. Their lesions have been reported to contain increased amounts of the neurohumors, acetylcholine and norepinephrine, as well as increased activity of acetylcholinesterase and catechol-O-methyltransferase. In vitro studies of epidermis show that beta adrenergic agonists fail to evoke the normal inhibition of mitosis of basal cells of patients with atopic dermatitis. Epidermis removed not only from the lesions, but also from normal-appearing skin, responded abnormally. The increase in intracellular levels of cAMP after exposure to catecholamines was similar in normal and atopic epidermis. Lymphocytes and PMN leukocytes isolated from patients with atopic dermatitis show both a decreased physiologic response (glycogenolysis and inhibition of lysosome enzyme release) and a decreased rise in intracellular levels of cAMP upon incubation with beta agonists, but a normal response to PGE1. Cortisol increases the response of lymphocyte adenyl cyclase to both agonists and, in the case of the patients with atopic disease, more than overcomes the depressed response to beta agonists. Because the leukocytes respond normally to PGE1 and because others have reported normal activities of skin and adenyl cyclase, phosphodiesterase, and protein kinases, we conclude that the step responsible for the diminished beta adrenergic response lies antecedent to the catalytic site of adenyl cyclase.
J Invest Dermatol 1976 Sep
PMID:Adrenergic mechanisms and the adenyl cyclase system in atopic dermatitis. 0 56

1. Guanylate cyclase of every fraction studied showed an absolute requirement for Mn2+ ions for optimal activity; with Mg2+ or Ca2+ reaction was barely detectable. Triton X-100 stimulated the particulate enzyme much more than the supernatant enzyme and solubilized the particulate-enzyme activity. 2. Substantial amounts of guanylate cyclase were recovered with the washed particulate fractions of cardiac muscle (63-98%), skeletal muscle (77-93%), cerebral cortex (62-88%) and liver (60-75%) of various species. The supernatants of these tissues contained 7-38% of total activities. In frog heart, the bulk of guanylate cyclase was present in the supernatant fluid. 3. Plasma-membrane fractions contained 26, 21, 22 and 40% respectively of the total homogenate guanylate cyclase activities present in skeletal muscle (rabbit), cardiac muscle (guinea pig), liver (rat) and cerebral cortex (rat). In each case, the specific activity of this enzyme in plasma membranes showed a five- to ten-fold enrichment when compared with homogenate specific activity. 4. These results suggest that guanylate cyclase, like adenylate cyclase, and ouabain-sensitive Na+ + K+-dependent ATPase (adenosine triphosphatase), is associated with the surface membranes of cardiac muscle, skeletal muscle, liver and cerebral cortex; however, considerable activities are also present in the supernatant fractions of these tissues which contain very little adenylate cyclase or ouabain-sensitive Na+ + K+-dependent ATPase activities.
Biochem J 1976 Sep 01
PMID:Guanylate cyclase. Subcellular distribution in cardiac muscle, skeletal muscle, cerebral cortex and liver. 1 Aug 90

1. The activities of the enzymes involved in the metabolism of cyclic nucleotides were studied in sarcolemma prepared front guinea-pig heart ventricle; the enzyme activities reported here were linear under the assay conditions. 2. Adenylate cyclase was maximally activated by 3mM-NaF; NaF increased the Km for ATP (from 0.042 to 0.19 mM) but decreased the Ka for Mg2+ (from 2.33 to 0.9 mM). In the presence of saturating Mg2+ (15 mM), Mn2+ enhanced adenylate cyclase, whereas Co2+ was inhibitory. beta-Adrenergic amines (10-50 muM) stimulated adenylate cyclase (38+/-2%). When added to the assay mixture, guanyl nucleotides (GTP and its analogue, guanylyl imidophosphate) stimulated basal enzyme activity and enhanced the stimulation by isoproterenol. By contrast, preincubation of sarcolemma with guanylyl imidodiphosphate stimulated the formation of an 'activated' form of the enzyme, which did not reveal increased hormonal sensitivity. 3. The guanylate cyclase present in the membranes as well as in the Triton X-100-solubilized extract of membranes exhibited a Ka for Mn 2+ of 0.3 mM; Mn2+ in excess of GTP was required for maximal activity. Solubilized guanylate cyclase was activated by Mg2+ only in the presence of low Mn2+ concentrations; Ca2+ was inhibitory both in the absence and presence of low Mn2+. Acetylcholine as well as carbamolycholine stimulated membrane-bound guanylate cyclase. 4. Cylic nucleotide phosphodiesterase activities of sarcolemma exhibited both high-and low-Km forms with cyclic AMP and with cyclic GMP as substrate. Ca2+ ions increased the Vmax. of the cyclic GMP-dependent enzyme.
Biochem J 1976 Sep 15
PMID:Adenylate cyclase, guanylate cyclase and cyclic nucleotide phosphodiesterases of guinea-pig cardiac sarcolemma. 1 Aug 95

Electrophysiological and mechanical effects of histamine were observed in guinea-pig papillary muscle which had been depolarized and rendered inexcitable by elevation of potassium concentration in Tyrode solution to 27 mM. 1. Histamine (3 X 10(-7) to 3 X 10(-5) M) restored the action potential and tension development. The amplitude of the action potential was increased by 31.6 mV/10-fold increase in extracellular Ca2+ concentration. Nifedipine (10(-6) M) abolished the electrical and mechanical responses which had been restored by histamine (10(-5) M) but TTX (10(-5) M) did not affect them. Reduction of the extracellular Na+ concentration to one half decreased the amplitude and the maximum rate of rise of the action potential restored by histamine (10(-5) M) while the peak tension was increased and an after-contraction occurred. 2. The maximum rate of rise and the amplitude of the action potential restored by histamine (10(-5) M) decreased with increase in stimulus frequency from 0.1-1.6 Hz. The peak tension decreased and then increased. The shape of the developed tension was also changed. In the presence of caffeine (1 mM), the only effect of an increase in stimulus frequency was a decrease in peak tension but the change in the shape of developed tension did not occur. 3. The electrical and mechanical responses restored by histamine (3 X 10(-6) or 10(-5) M) were depressed by metiamide (3 X 10(-6) M) but not by diphenhydramine (10(-5) M) or bufetolol (10(-6) M). 4. The electrical response restored by histamine (10(-6) or 10(-5) M) was enhanced by papaverine (10(-5) M) and depressed by N-methylimidazole (10 mM). It is concluded that histamine may enhance the slow inward Ca2+ current mediated by histamine H2-receptors and the adenylate cyclase system in ventricular muscle and that the positive inotropic action of histamine may be attributed to these mechanisms.
Naunyn Schmiedebergs Arch Pharmacol 1976 Sep
PMID:Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium. 1 80

Injection of tranylcypromine and L-tryptophan results in rats displaying behavioural changes including hyperactivity, probably due to stimulation of post-synaptic 5-hydroxytryptamine (5-HT) receptors. Increased locomotor activity of a different type is elicited by injection of tranylcypromine and L-dopa, a procedure which increased dopaminergic function in the brain. It has now been demonstrated that the neuroleptic drugs, chlorpromazine, alpha-flupenthixol, haloperidol and spiroperidol block both syndromes. The inhibition produced by these drugs on 5-HT-induced hyperactivity is probably because a dopaminergic system is involved in the behavioural expression of the 5-HT induced hyperactivity. The structurally related drugs with no neuroleptic activity (ethopropazine, promethazine and beta-flupenthixol)are without effect on thses hyperactivity syndromes. Also ineffective were the neuroleptics pimozide and clozapine. Striatal dopamine sensitive adenylate cyclase activity in vitro was inhibited by the administration of chlorpromazine (100 mg/kg) in vivo. Rats treated for 4 or more days with chlorpromazine, alpha-flupenthixol, spiroperidol and haloperidol subsequently showed enhanced locomotor activity in response to tranylcypromine and L-Dopa. Administration of those drugs which did not block hyperactivity acutely did not result in enhancement. Only chlorpromazine, when given for 4 days, enhanced the hyperactivity response following tranylcypromine and L-tryptophan, probably because the drug also blocks 5-HT receptors. In rats displaying enhanced behavioural responses no evidence was found for enhanced sensitivity of striatal adenylate cyclase to dopamine.
Psychopharmacology (Berl) 1976 Sep 29
PMID:Single and repeated administration of neuroleptic drugs to rats: effects on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-Dopa. 1 27

Mutants of Escherichia coli K-12 lacking functional adenylate cyclase (cya) or the cyclic adenosine 3',5'-monophosphate (cAMP) receptor protein (crp) were compared with their wild type to evaluate the role played by the cAMP-cAMP receptor protein complex in regulating this organism's membrane-associated bioenergetic functions. Both mutants were found to be equally defective in carrying out various electron transport activities. In particular, their capacity for synthesizing a functional oxygen-linked transhydrogenase system was totally repressed, and their content of flavin adenine dinucleotide was reduced by approximately 85%. In addition, it was found that the mutant strains had a decreased ability to generate a protonmotive force and to use this chemiosmotic force to generate adenosine 5'-triphosphate. All these membrane-associated dysfunctions were completely restored to the wild-type state when the cya cells were grown in the presence of exogenous cAMP. As would be expected if these controls were operating at the transcriptional level, the crp cells retained the mutant character even when grown in the presence of this cyclic nucleotide.
J Bacteriol 1977 Sep
PMID:Cyclic adenosine 3',5'-monophosphate regulation of membrane energetics in Escherichia coli. 1 22


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