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)

Nucleotide metabolism was studied in rats during and following the induction of 10 min of forebrain ischemia (four-vessel occlusion model). Purine and pyrimidine nucleotides, nucleotides, and bases in forebrain extracts were quantitated by HPLC with an ultraviolet detector. Ischemia resulted in a severe reduction in the concentration of nucleoside triphosphates (ATP, GTP, UTP, and CTP) and an increase in the concentration of AMP, IMP, adenosine, inosine, hypoxanthine, and guanosine. During the recovery period, both the phosphocreatine level and adenylate energy charge were rapidly and completely restored to the normal range. ATP was only 78% of the control value at 180 min after ischemic reperfusion. Levels of nucleosides and bases were elevated during ischemia but decreased to values close to those of control animals following recirculation. Both the decrease in the adenine nucleotide pool and the incomplete ATP recovery were caused by insufficient reutilization of hypoxanthine via the purine salvage system. The content of cyclic AMP, which transiently accumulated during the early recirculation period, returned to the control level, paralleling the decrease of adenosine concentration, which suggested that adenylate cyclase activity during reperfusion is modulated by adenosine A2 receptors. The recovery of CTP was slow but greater than that of ATP, GTP, and UTP. The GTP/GDP ratio was higher than that of the control animals following recirculation.
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PMID:Mononucleotide metabolism in the rat brain after transient ischemia. 370 29

The occlusion of the terminal aortic region was experimentally induced in 48 dogs. It has been shown that myocardial lesions localized predominantly in the papillary muscles and subendocardially appear already 3 hours after the occlusion. The number of the affected cardiomyocytes increases and their size enlarges. The duration of ischemia directly correlates with metabolic disturbances: changes in the function of adenylate cyclase system, ion imbalance, damages in the energy metabolism. Metabolic and morphologic changes are accompanied by disturbances in the cardiac function manifested in the decrease of myocardial contractility.
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PMID:[Biochemical and morphofunctional changes in the myocardium of dogs with occlusion of the terminal portion of the aorta]. 380 43

This study was designed to correlate histopathological changes in gerbil brain following unilateral primary and secondary ischemia to enzymatic-adenylate cyclase damage. At three hrs permanent occlusion of the right common carotid artery only minimal histological changes were evident in cerebrum, hippocampus, striatum and olfactory tubercle while the enzyme responses were unremarkable. Severe histological and enzymatic alterations were present at one hour of recirculation subsequent to 3 hrs of unilateral occlusion. Similar damage was evident at 6 and 24 hrs permanent occlusion. Principal enzyme damage was directed toward basal activity, as well as stimulation of the catalytic (forskolin-sensitive) sites on the enzyme complex. For the most part the transducer (GTP-sensitive) site was unaffected by ischemia until 24 hr ligation. These changes were observed in only those gerbils developing severe symptoms of stroke.
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PMID:Adenylate cyclase and histopathological changes in the gerbil brain following prolonged unilateral ischemia and recirculation. 404 Jun 71

Five minutes of bilateral carotid occlusion in unanesthetized gerbils produced substantial changes in spontaneous locomotor activity. Behavior was decreased after 1 hr of reperfusion and was increased at 24 hrs post-ischemia. Adenylate cyclase activity was measured in homogenates of frontal cortex and hippocampus at 90 min and 24 hrs following 5 min of cerebral ischemia. Enzyme activity was determined in the absence and presence of the activators guanosine-5'-triphosphate (GTP), guanylyl-5'-imidodiphosphate (GppNHp), isoproterenol (Iso) plus GTP, and forskolin (Fors) plus GTP. Homogenates responded with expected increases over basal adenylate cyclase activity with addition of all activators. An additional small increase in isoproterenol-stimulated activity was observed in frontal cortex homogenates at 90 min post-ischemia. No other significant changes in adenylate cyclase activity were observed after either 90 min or 24 hrs of reperfusion. The substantial increases in locomotor activity evident at 24 hrs after transient ischemia are not associated with measurable changes in adenylate cyclase activity in homogenates of frontal cortex or hippocampus.
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PMID:Adenylate cyclase activity and motor behavior following cerebral ischemia in the unanesthetized gerbil. 404 Sep 98

Changes in the sensitivity of adenylate cyclase and steady-state levels of cyclic AMP (adenosine 3',5'-monophosphate) occur in mammalian brain during ischemic episodes. In our previous investigation with the gerbil model of bilateral ischemia there was an indication that ischemic conditions produced an enhancement of GTP sensitivity of adenylate cyclase within the cerebral cortex. The present study employed a kinetic analysis to evaluate further the role of this GTP modulation of adenylate cyclase in the gerbil frontal cortex during periods of bilateral ischemia and recirculation. In general, after either 15-min (with or without 15-min reflow) or 60-min ischemia the Vmax to GTP (alone or with dopamine and norepinephrine) was increased. Under these conditions the ED50 for half-maximal enzyme activation was decreased, indicating a greater affinity of the transducer site for GTP during ischemia. However, if irreversible 60-min ischemia was followed by 15-min reflow the enzyme responses to GTP were now absent. An unexpected observation showed that the ED50 for GTP activation of cortical adenylate cyclase was likewise attenuated when sham-operated animals were compared to normal gerbils.
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PMID:Kinetics of GTP-modulation of adenylate cyclase in gerbil cerebral cortex after bilateral ischemia. 609 73

The incubation of adult mouse skin pieces in a buffered salts medium at 37 degrees C led to a rapid accumulation of cyclic adenosine 3'5-monophosphate (cyclic AMP) in the tissue. In mouse skin maximum accumulation occurred after 2 min incubation; levels reverted to near control levels after a further 7 min incubation. the increase in cyclic AMP contents of the skin pieces was probably not due to the release of materials which activate adenylate cyclase after binding to cellular receptors. Thus, cyclic AMP accumulation was unaffected by the inclusion of alpha- or beta-adrenergic antagonists, or by the pretreatment of adult mouse skin with indomethacin (an inhibitor of prostaglandin synthetase). Furthermore, adenosine, a known activator of epidermal adenylate cyclase, could not be detected in the incubation medium. The functional integrity of epidermal adenylate cyclase was maintained during the cyclic AMP accumulation in response to ischemia. Thus, adenosine, histamine, isoproterenol and prostaglandin E2 (PGE2) augmented the cyclic AMP response. Cyclic AMP accumulation at 37 degrees C was not observed in newborn mouse skin; this lack of cyclic AMP accumulation was probably not due to increased activity of low affinity cyclic AMP phosphodiesterase in newborn mouse skin.
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PMID:The effect of ischemia on cyclic adenosine 3',5'monophosphate accumulation in mouse skin. 627 64

We have investigated alterations in sarcolemmal function that occur during myocardial ischemia. Rabbit ventricles were incubated at 37 degrees C for time periods ranging from 5 min to 2 h. The ischemic tissue was homogenized, and activities of the sarcolemmal enzymes Na+-K+-ATPase, K+-p-nitrophenylphosphatase (K+-pNPPase), and adenylate cyclase were measured in the crude homogenate. Na+-K+-ATPase and K+-pNPPase were substantially inhibited after only 10 min of ischemia, and activities for all three enzymes declined progressively up to 1 h of ischemia, when activities were 37-59% of control. Highly purified sarcolemmal membranes prepared from control tissue and myocardium that had been made ischemic for 1 h showed similar purification of sarcolemmal enzymes, passive Ca2+ binding, and passive permeability to Ca2+. However, the velocity of Na+-Ca2+ exchange in ischemic sarcolemmal vesicles was reduced approximately 50% due to a reduction in Vmax. Although the parallel decline in activities of several sarcolemmal functions might suggest a change in membrane structure, phospholipid and cholesterol contents in ischemic sarcolemma were the same as control.
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PMID:Sodium-calcium exchange and sarcolemmal enzymes in ischemic rabbit hearts. 628 34

Cyclic AMP-dependent protein kinase isozymes of pig and human skin (epidermis) were separated by DEAE-cellulose column chromatography after micromodification for small biopsy samples. Clear-cut separations of type I and type II isozymes, which were of about equal amounts, could be obtained only when the ischemia effect was avoided by in vivo freezing of skin and homogenization for less than 10 s. Intradermal injections of epinephrine caused dose-dependent activation of type I isozyme, but not of type II. Injections of other skin adenylate cyclase stimulators such as histamine, adenosine, and prostaglandin E2 elevated the local cyclic AMP levels to not more than 5 pmol/mg protein and also stimulated only the type I isozyme. Incubation of keratome-sliced pig skin under various conditions caused both activation by dissociation and inactivation by reassociation of the subunits, which appeared to be dependent on the cyclic AMP content. Epinephrine added to the incubation medium led to complete activation of both type I and type II isozymes (the intraepidermal cyclic AMP contents ranged from 20-50 pmol/mg protein). The isozymes of normal skin and involved skin of psoriatics showed identical peaks of type I and type II isozymes of equal amounts. The data indicate that protein kinase in the involved skin is not in an activated (by cyclic AMP) state.
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PMID:Cyclic AMP-dependent protein kinase isozymes of pig skin and human skin from normal and psoriatic subjects. 629 36

Bilateral ischemia induced by occlusion of the carotid arteries for 5 min causes a selective degeneration of CA 1 neurons of the hippocampus of Mongolian gerbils. The degeneration process is complete in 14 days as assessed by light microscopy. After one week, basal values for radioactive cyclic AMP in [3H]adenine-labeled tissue from the CA 1 region of hippocampus are greatly reduced as are the absolute magnitude of accumulations of cyclic AMP elicited by norepinephrine, 2-chloroadenosine and histamine. At 2 and 4 weeks, basal values for radioactive cyclic AMP have nearly attained control values and the response to 2-chloroadenosine is fully restored. The response of cyclic AMP-generating systems to norepinephrine is now significantly greater than in control, while the response to histamine remains reduced in magnitude. The ischemia has no effect on basal values for radioactive cyclic AMP or on responses in [3H]adenine-labeled slices from cerebral cortex. Histamine levels after ischemia are significantly increased above control in the CA 1 region. Basal and histamine-sensitive adenylate cyclase activity in the membrane preparations are slightly decreased during the first week after ischemia, followed by a recovery. There is an inverse correlation between histamine levels and adenylate cyclase activity in individual animals 4 days after ischemia.
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PMID:Degeneration of CA1 neurons in hippocampus after ischemia in Mongolian gerbils: cyclic AMP-systems. 630 59

The effect of three modes of anesthesia was evaluated with regard to regional damage to central cyclic nucleotide systems in the gerbil brain as a consequence of bilateral ischemia (clamping the common carotids) followed by various periods of recirculation. The injection of thiopental as much as 90 min before stroke prevented damage to chemical activation [catecholamines, guanosine triphosphate (GTP), or forskolin] of adenylate cyclase. However, the basal enzyme activity was lower in all brain regions whether thiopental was administered to stroke or sham-operated animals. Injection of ketamine drastically shortened the survival times of gerbils undergoing stroke followed by recirculation. About 90% of the animals could tolerate a maximum of only 15 min stroke with 15 min recirculation. At this time frame the patterns of activation of adenylate cyclase in only the olfactory tubercle and hippocampus were altered. When procaine was used as a local anesthetic agent during surgery, damage to catecholamine-, GTP-, or forskolin-activated adenylate cyclase was evident to varying degrees in the frontal cortex, hippocampus or olfactory tubercle, but not in the nucleus accumbens and olfactory bulb of gerbils subjected to 60-min stroke followed by 15 or 150 min of recirculation. The degree of enzyme damage was neither correlated with the fed vs. fasted state of the animal nor with the whole blood concentration of glucose. A depression in the amplitude of visually evoked potentials correlated to neurological signs and to enzyme damage. During anesthesia, ketamine increased steady-state concentrations of cyclic AMP in the frontal cortex and hippocampus from gerbil brains that had been rapidly inactivated by microwave irradiation. Thiopental increased steady-state cyclic AMP in only the olfactory tubercle. Cyclic GMP concentrations were unchanged by any anesthetic agent. In animals completely recovering from anesthesia and occluded for a brief period followed by 10 min of reflow, steady-state concentrations of only cyclic AMP were augmented.
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PMID:Regional cyclic AMP systems during secondary ischemia in gerbils: influence of anesthetic agents. 632 54


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