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)

Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism.
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PMID:[Cyclic adenosine monophosphate and atherogenic factors]. 20 91

Acute severe myocardial ischemia and evolving myocardial infarction cause neural stimulation, increased levels of circulating catecholamines, and release of catecholamines from storage depots in the left ventricle, with consequent exposure of injured myocardial cells to relatively high concentrations of catecholamines during the transitional period in which myocyte injury becomes progressively more severe. beta-Adrenergic receptor numbers may be increased in the ischemic myocardium within 15-35 minutes of coronary artery occlusion and are associated with intact or enhanced coupling with the adenylate cyclase enzyme and elevated levels of cyclic adenosine monophosphate (AMP); their stimulation may mediate ventricular fibrillation. The administration of beta-adrenergic blockers before or within the first few minutes after coronary artery occlusion prevents or attenuates the development of ventricular fibrillation. beta-Receptor numbers are increased in the ischemic myocardium at 60 minutes of coronary artery occlusion but are uncoupled from the adenylate cyclase enzyme at the level of the G protein and/or catalytic unit. However, with reperfusion after 60 minutes of coronary artery occlusion, the increase in ischemic-region beta-adrenergic receptor numbers persists, and adenylate cyclase responsiveness to beta-receptor stimulation is restored. If a catecholamine is administered, increases in cyclic AMP and activated phosphorylase occur in ischemic-reperfused myocardium. These data indicate that beta-adrenergic mechanisms may play an important role in arrhythmogenesis and may contribute to myocyte injury during severe and intense myocardial ischemia and evolving myocardial infarction.
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PMID:Alterations in beta-adrenergic receptors, adenylate cyclase, and cyclic AMP concentrations during acute myocardial ischemia and reperfusion. 197 23

Picotamide is the most interesting compound of 4-OH isophthalic acid. It is effective in vitro and in vivo. Picotamide induces inhibition of platelet aggregation: it is a thromboxane synthetase inhibitor and a thromboxane receptor antagonist. Picotamide causes cyclic endoperoxide accumulation and diverts their metabolism toward PgI2 synthesis in endothelial cells. PGI2 stimulates the adenylate cyclase with cAMP synthesis which makes platelets less sensitive to aggregatory stimulation. Picotamide induces enhancement of fibrinolytic activity, with significant reduction in the level of circulating plasminogen but in the same time it does not affect antithrombin III and FDP levels. In the present study picotamide or placebo were administered in a double blind trial at 600 mg daily for six months to 51 patients effected by diabetic macro and/or microangiopathy. The patients were 38 men and 13 women, the age was between 20 and 80 years (mean age 62.34). Twenty-seven patients were affected by type I diabetes and 24 by type II diabetes. Twenty-three of these patients presented macro-angiopathic lesions, 9 only microangiopathic lesions and 13 both. Twenty-five patients received picotamide and the other 25 an identical placebo for six months. One patient manifested myocardial infarction during the wash-out period and failed to enter the study. The following determinations were carried out: at T0 clinical examination, Doppler ultrasonography, Winsor Index, laboratory parameters; after 90 days (T90) clinical examination and Winsor Index and after 180 days (T180) were repeated photoplethysmography and clinical parameters too. Patients were not only evaluated for the vascular disease of lower extremities, but also for the other complications of diabetes, as retinopathy, nephropathy, cardiac and cerebrovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Picotamide: prevention and therapy of diabetic vasculopathies. A double-blind clinical study]. 214 11

Augmented sensitivity to sympathetic mediators occurs in non-infarcted tissues after healing of myocardial infarction. We studied regional beta-adrenergic receptor numbers and adenylate cyclase activity in cat ventricles with healed myocardial infarctions and in the same regions from control hearts. Tissues were obtained from regions remote from and adjacent to the infarct and from the infarct zone itself. Beta-adrenergic receptor numbers were significantly reduced in adjacent and infarcted regions of the healed infarction model. Basal adenylate cyclase activity was increased in tissues remote from and adjacent to the infarct. In remote tissues, total adenylate cyclase activity during maximum isoproterenol stimulation was increased, but the isoproterenol stimulated increment was normal after subtraction of basal activity. In adjacent tissues, total adenylate cyclase activity during isoproterenol stimulation was normal, but the stimulated increment was reduced after subtraction of basal activity. This reduction in activity was reversed when GTP was replaced with Gpp(NH)p. No changes in adenylate cyclase activity, relative to control, were observed in tissues from the infarcted area. These results indicate that chronic changes in the beta-adrenergic receptor/adenylate cyclase system persist after healing of myocardial infarction, and that the nature of the changes are regional depending on proximity to the healed scar.
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PMID:Regional beta-adrenergic receptors and adenylate cyclase activity after healing of myocardial infarction in cats. 216 93

Cocaine can induce lethal cardiovascular events, including myocardial infarction and ventricular fibrillation. The mechanisms responsible for these cardiotoxic effects of cocaine remain largely to be determined. Cocaine has both sympathomimetic (inhibition of neuronal uptake of norepinephrine) and local anesthetic (Na+ channel blockade) properties. Neurotransmitters released from cardiac sympathetic nerves bind to both alpha- and beta-adrenergic receptors eliciting a cascade of intracellular responses. Stimulation of beta-adrenergic receptors activates adenylate cyclase, increasing cyclic AMP levels, whereas alpha-adrenergic receptor stimulation activates phospholipase C, increasing inositol trisphosphate. These second messengers, in turn, elicit increases in cystolic calcium. Elevations in cystolic calcium can provoke oscillatory depolarizations of the cardiac membrane, triggering sustained action potential generation and extrasystoles. Cocaine also acts as a local anesthetic by inhibiting sodium influx into cardiac cells, which impairs impulse conduction and creates an ideal substrate for reentrant circuits. Thus, the adrenergic and anesthetic properties of cocaine could act synergistically to elicit and maintain ventricular fibrillation. Adrenergic receptor activation would trigger the event whereas sodium channel blockade would create the reentrant substrate to perpetuate the malignant arrhythmias.
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PMID:Mechanisms responsible for the cardiotoxic effects of cocaine. 218 73

Ventricular hypertrophy should be divided into at least physiologic and patholgic states in order to clarify structural and functional clinical alterations. The elucidation of the structural, functional, and biochemical mechanisms of ventricular hypertrophy is vital to designing effective preventive and therapeutic measures for the hypertensive patient. Tissue markers may help differentiate pathologic from physiologic hypertrophy. Studies have established the concept that norepinephrine may be a myocardial cellular hypertrophying hormone. The studies ranged from the direct application of norepinephrine to isolated myocardial cells to the chronic subhypertensive infusion of norepinephrine into the conscious, free-roaming dog. Norepinephrine infusion can produce physiologic ventricular hypertrophy or a pathologic state of hypertrophic cardiomyopathy, the former by a three- to four-month infusion and the latter by an infusion of more than six months. The biochemical effect of subhypertensive infusion of norepinephrine was studied prior to the production of ventricular hypertrophy, thereby permitting the elucidation of the mechanism of the hypertrophic process. The biochemical stimulus for the production of myocardial cellular hypertrophy is postulated to be a diminution of cyclic AMP and a stimulation of alpha-1 receptors. Because the ventricular septum has the highest content of adenylate cyclase, which does not increase with cyclic AMP, these changes are postulated to be the biochemical basis for septal hypertrophy in the disease entity hypertrophic cardiomyopathy. A unique conscious-canine model for the production of a myocardial infarction capable of creating a controlled localized occlusion of the coronary artery is presented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chronic infusion of norepinephrine on cardiac structure, function, and biochemistry: physiologic versus pathologic hypertrophy. 253 29

Distinct increase and then decrease in content of cyclic nucleotides was observed in dog myocardium ventricles and auricles within early periods of heart infarction (10 min-4 hrs). Within a day after ligation of artery the ratio cAMP/cGMP was considerably decreased as a result of activation of guanylate cyclase and cAMP-phosphodiesterase as well as due to a decrease in activity of adenylate cyclase. Acute ischemia of small area of the heart left ventricle caused impairment of cyclic nucleotide metabolism in all the heart muscle.
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PMID:[The cyclic nucleotide system in various sections of the dog myocardium in experimental infarction]. 256 32

Cyclic AMP and cyclic GMP content and activities of cyclic nucleotide metabolic enzymes were determined in intima and media of atherosclerotic and unaffected human aorta obtained shortly after death due to myocardial infarction. Cyclic AMP content in fatty streaks and atherosclerotic plaques was lower by three- and five-fold, respectively, as compared with uninvolved intima. Cyclic GMP level in atherosclerotic lesions was estimated to be three-fold higher than in grossly normal area. Basal activity of adenylate cyclase in fatty streaks and plaques was two- to six-fold lower than in unaffected intima. Besides, the ability of adenylate cyclase to be stimulated by the stable analogue of prostacyclin, carbacyclin, was suppressed in plaques. Guanylate cyclase activity in fatty streaks was 1.5- to three-fold higher than in normal tissue. The thiol-reducing agent, dithiothreitol, decreased the enzyme activity to normal level, suggesting the oxidative nature of guanylate cyclase activation in the lesion zone. There were no significant changes in cyclic AMP phosphodiestease activity in the regions of the atherosclerotic lesion. Cyclic GMP phosphodiesterase activity in atherosclerotic plaques was two-fold lower than in the intima of unaffected areas. We did not find differences in the content of cyclic nucleotides or related enzyme activities in the media of uninvolved areas of human aorta nor in the media underlying atherosclerotic lesions. Our findings suggest that development of human atherosclerotic lesions is accompanied by dramatic changes in the cyclic nucleotide metabolism featuring gradual hormonal receptor uncoupling from adenylate cyclase, activation of guanylate cyclase in fatty streaks and inhibition of cyclic GMP phosphodiesterase in plaques.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disorders in the system of cyclic nucleotides in atherosclerosis: cyclic AMP and cyclic GMP content and activity of related enzymes in human aorta. 288 18

The mechanisms underlying the non-competitive beta-antagonistic properties of amiodarone were investigated, and the haemodynamic responses to exercise following the administration of oral amiodarone or intravenous propranolol were compared in dogs with a healed myocardial infarction submitted to a graded treadmill exercise. In radioligand binding studies, amiodarone, up to 10 mumol/L did not compete with 125I-iodocyanopindolol for binding to rat heart beta-adrenoceptors. Exposure of cardiac membranes to greater concentrations of amiodarone induced a significant decrease in the number of beta-adrenoceptors without affecting their affinity for 125I-iodocyanopindolol. Similar results were observed ex vivo, in rats after single or multiple dose administration. When added in vitro to rat heart membranes, amiodarone non-competitively inhibited the activation of adenylate cyclase by isoprenaline, glucagon and secretin. Stimulation of adenylate cyclase by those agents which act at more internal sites in the sarcolemmal membrane such as GppNHp, sodium fluoride or forskolin, was much less affected by amiodarone. In dogs performing at a submaximal work level, amiodarone significantly reduced heart rate and tended to increase coronary flow and to reduce left ventricular end-diastolic pressure, but did not affect left ventricular dP/dt. During submaximal exercise, propranolol had similar effects on heart rate, but dramatically reduced myocardial contractility.
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PMID:Amiodarone. Biochemical aspects and haemodynamic effects. 298 37

Angiotensin converting enzyme (ACE) inhibitors are not known to have a direct effect on the myocardium. However, there is some evidence to suggest that they can play an important role in protecting the heart during the evolution of hypertensive and coronary arterial disease, both acutely and on a long term basis. Reduction of afterload by balanced arterial and venular dilatation has led to a sustained improvement of cardiac performance both in hypertension and heart failure. Reversal of cardiac hypertrophy has been shown to restore inotropic responsiveness to stimulators of the adenylate cyclase system. Following myocardial infarction, captopril has prevented undue ventricular dilatation and normalized left ventricular chamber stiffness; this prevented deterioration of cardiac function and improved long term survival after infarction. Control of secondary aldosteronism and prevention of hypokalaemia can play an important role in the prevention of cardiac arrhythmias. The lack of reflex sympathetic stimulation during long term captopril therapy can also play a favourable role in that respect. Although highly speculative, evidence is accumulating that ACE inhibition could have a cardioprotective effect in acute myocardial ischaemia. It is based on the demonstration that renin can be produced by myocardial cells, that angiotensin is liberated by the ischemic myocardium and that angiotensin in high renin conditions plays an active constrictor role in regulating the coronary circulation.
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PMID:Prospectives for angiotensin converting enzyme inhibition in heart diseases. 300 6


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