Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animals develop 'infarct-like' lesions when injected with isoproterenol (ISP), a potent synthetic catecholamine. These lesions are morphologically similar to those of 'coagulative myocytolysis' (COAM) or myofibrillar degeneration, one of the findings described in acute myocardial infarction and sudden death in man. Wistar rats were divided into 8 groups: some were injected with 10 mg/kg ISP i.p. plus 5 muCi of tritiated ISP, while others served as control. Animals were sacrified at 5 and 30 min and 24 and 72 h. The ISP-induced lesions were studied by means of light microscopy, histochemistry, autoradiography and electron microscopy. Myofibrillar degeneration, positive tests for ischemia, increase of succinic dehydrogenase enzymes, hypercontraction and widening of Z bands of sarcomers were correlated with the rapid distribution of ISP. These lesions were minimized by prenylamine, a drug which inhibits catecholamine effects by slowing down Ca transport. It is concluded that myocardial necrosis induced by ISP is probably due to a primary act on the sarcolemmal membrane, followed by stimulation of adenylate cyclase, activation of Ca and Na channels, exaggreated Ca inflow, excess of excitation-contraction coupling mechanism, energy consumption and cellular death. The close resemblance of human COAM to ISP-induced lesions suggests that similar mechanisms may be involved.
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PMID:Pathogenesis of isoproterenol-induced myocardial lesions: its reation to human 'coagulative myocytolysis'. 63 73

To determine the effects of chronic myocardial infarction on beta-adrenergic properties of canine myocardium, the hearts of nine mongrel dogs were studied 3 weeks after acute myocardial infarction. Infarction was produced by ligating the left anterior descending coronary artery in five dogs and the circumflex artery in four dogs. The heart was divided into normal and infarct zones (either anterior or posterior, depending on the vessel ligated) and marginal zones (septal and lateral), each zone being subdivided into epicardial and endocardial portions. Myocardial blood flow (microsphere technique) was markedly reduced in the infarct zone. In eight endocardial infarct samples after left anterior descending ligation, the maximal number (+/- SD) of binding sites assessed by 125I-iodocyanopindolol was 3.9 +/- 1.9 pmol/mg deoxyribonucleic acid (DNA) and was reduced from normal endocardial values (9.7 +/- 9.4 pmol/mg DNA, p less than 0.05). The dissociation constant (Kd), which is a measure of the affinity of the iodinated antagonist for the receptor, did not differ (304 +/- 222 versus 338 +/- 219 pM, p = NS). In the epicardium, the maximal number of beta-adrenergic receptors was also reduced (p less than 0.05), without a change in Kd. In the lateral and septal zones neither the maximal number of binding sites nor Kd values differed from those of normal endocardium. In nine endocardial infarct zones, (-)-isoproterenol-stimulated adenylate cyclase activity was reduced compared with control (34,870 +/- 29,430 versus 88,660 +/- 63,640 pmol/mg DNA/30 minutes, p less than 0.01), but the ratio of (-)-isoproterenol-stimulated to maximal (sodium fluoride-stimulated) adenylate cyclase activity was unchanged between normal and infarct zones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenergic receptor properties of canine myocardium: effects of chronic myocardial infarction. 301 63

Metabolism of arachidonic acid (AA) in blood platelets and in vascular endothelium does not lead to prostaglandins, but thromboxane A2 and prostacyclin are generated. These labile metabolites of AA antagonize each other: thromboxane A2 is a vasoconstrictor and proaggregatory agent, whereas prostacyclin dilates arteries, prevents platelets from aggregation, and dissipates the preformed platelet clumps. Prostacyclin is a powerful stimulator of adenylate cyclase in platelets and therefore its antiplatelet action is potentiated by phosphodiesterase inhibitors such as theophylline or dipyridamole. Cyclo-oxygenase of AA is inhibited by aspirin, thromboxane synthetase by analogues of prostaglandin endoperoxides, and prostacyclin synthetase by linear lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxydation in the body and the subsequent molecular damage to prostacyclin synthetase in the rheologically determined areas of arterial walls. Endothelium deprived of prostacyclin is the basis for microthrombi formation, and follows a sequence of events described by Rokitansky and later by Ross. Prostacyclin is also a circulating hormone which is generated by the lungs. Thereby a damage of this "endocrine gland" by respiratory disorders, air pollution, or tobacco smoking are likely to contribute to pathogenesis of atherosclerosis, myocardial infarction, and arterial thromboembolism. Pharmacological treatment and prevention of these diseases should logically include antioxydants, prostacyclin and its analogues, thromboxane synthetase inhibitors and perhaps cyclooxygenase inhibitors (aspirin ?). Prostacyclin was already infused intravenously to men and its powerful antiaggregatory and deaggregatory actions were demonstrated. These properties of prostacyclin along with its vasodilator and positive inotropic actions destine this hormone to be a new type of antithrombotic drug in acute myocardial infarction.
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PMID:Prostaglandins, platelets, and atherosclerosis. 677 Nov 2

Metabolic effects of dexamethasone (DX) on the noninfarcted functioning myocardium were studied in rabbits with experimental coronary artery ligation to evaluate the usefulness of glucocorticoids in acute myocardial infarction. Maximum active tension of noninfarcted area of the isolated perfused hearts was markedly reduced 6 hr, 2 days, and 5 days after ligation, associated with significant decreases in norepinephrine (NE) and cAMP contents, but with no changes in adenylate cyclase (AC) and cAMP phosphodiesterase (PDE) activities. Calcium content of mitochondrial fraction was considerably increased in the peri- and noninfarcted area without any changes in microsomal CA2+ or myocardial total Ca2+. Ca2+ uptake rate and Ca2+-dependent ATPase activity of the sarcoplasmic reticulum fraction from the operated hearts were markedly reduced. Intramuscular administration of DX (3 mg/kg body wt/day) for 2 days after operation significantly improved these reductions in myocardial function and metabolism. In normal hearts from animals without infarction, DX caused 48% elevation in basal cAMP level, marked reductions in mitochondria and microsomal Ca2+, and 26% decrease in PDE activity, although no changes in myocardial total Ca2+ AC activity and myocardial contractility were observed. NE-induced inotropic effects were markedly enhanced in both control and operated groups with DX treatment. These results indicated that large doses of DX would improve the reduced myocardial function and metabolism in acute myocardial infarction by increasing basal cAMP level and by its influence on intracellular Ca2+ available for cellular activity.
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PMID:The effects of large doses of dexamethasone on myocardial contractility and calcium metabolism in experimental myocardial infarction. 742 58

Ultra-high-frequency dielectrometry was used to determine the dielectric permeability of erythrocyte suspension cell membranes in 48 patients with acute myocardial infarction who were given agonists, antagonists, and modulators of the adenylate cyclase system. The study showed that the functional status of erythrocyte membranes changed correlating with the clinical course of the disease. Changes in this status were followed by complications of improvement. It was evidenced that the trend of a pathological process in coronary stress was associated with the functional status of erythrocyte membranes. Ultra-high-frequency dielectrometry is a sensitive method for evaluating the status of patients with myocardial infarction, controls the natural history of the diseases at the molecular level and to predict the development of complications.
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PMID:[The molecular cellular aspects in predicting the course of an acute myocardial infarct]. 814 26