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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electrophysiological effect of 5'-adenosine monophosphate (AMP) was examined in isolated atrial myocytes of guinea pig. Membrane potential and ionic currents were measured by the tight-seal, whole-cell patch-clamp technique. AMP caused the shortening of atrial action potential in a dose-dependent manner. In voltage-clamp experiments, AMP (3-10 microM) caused the activation of IKACh as well as the decrease in basal ICa. Prolongation of action potential duration caused by isoproterenol (20 nM) was antagonized by AMP (10 microM). Isoproterenol (20 nM) occasionally caused the sustained rhythmic activity and the subsequent application of AMP (10 microM) terminated it. AOPCP (10 microM), which inhibits 5'-nucleotidase and hence prevents breakdown of AMP, did not significantly attenuate the effect of AMP on shortening action potential. However, the application of adenosine deaminase (1 U/ml), which deaminates adenosine to inosine, partially reversed the shortening of action potential caused by AMP (10 microM). These results indicate that (1) AMP could activate IKACh and decrease basal ICa simultaneously, and antagonize the isoproterenol-stimulated action potential prolongation; and (2) the observed electrophysiological effect of AMP in whole-cell preparation is attributed to AMP per se as well as its degradative product, adenosine.
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PMID:Evidence of direct activation of adenosine A1 receptor by 5'-adenosine monophosphate in isolated guinea pig atrial myocytes. 162 79

Fat-cells were isolated from patients of body-mass indices (BMIs) ranging from 17.9 to 83.9 kg/m2. Isoprenaline-stimulated cyclic AMP accumulation in cells prepared from obese subjects as compared with normal-weight subjects, was less sensitive to inhibition by the adenosine agonist N6-(phenylisopropyl)adenosine (PIA) (P = 0.047). The inhibition of 7 beta-desacetyl-7 beta-[gamma-(N-methylpiperazino) butyryl]-forskolin-stimulated adenylate cyclase by PIA in the presence of adenosine deaminase was also much attenuated in crude plasma membranes of adipocytes prepared from massively obese patients as compared with lean controls (P = 0.0143). This difference was probably not due to different cell size, because adenylate cyclase of crude plasma membranes of large adipocytes was actually more sensitive to PIA than was adenylate cyclase of membranes of smaller fat-cells co-isolated from the same individual. The stimulatory effect of PIA on glucose uptake in the presence of adenosine deaminase was depressed in adipocytes prepared from obese subjects and correlated with BMI at r = -0.626 (P = 0.007) at 100 nM-PIA. The adenosine receptors were studied by using the adenosine antagonist 1,3-[3H]dipropyl-8-cyclopentylxanthine. The binding was rapid and proportional to protein concentration. There was no difference in the affinities of receptors in membranes of obese and normal-weight subjects; Kd values of all patients averaged 3.3 nM. Bmax values were 54 and 130 fmol/mg of protein in membranes prepared from seven obese and five control patients respectively. The Bmax values calculated per mg of protein correlated with BMI at r = -0.539 (P = 0.047). The adenosine content of adipose tissue was higher in obese than in control subjects. These results demonstrate an attenuated response of cyclic AMP accumulation, adenylate cyclase and glucose uptake to adenosine in fat-cells prepared from obese subjects, and suggest that this change is at least partly due to changes in the amount of adenosine receptors, but not their affinity. The decreased receptor number could be due to higher adenosine content. A higher adenosine concentration in adipose tissue could explain why lipolysis is inhibited in situ in obesity, and the desensitization could explain the diminished response to adenosine analogues in isolated fat-cells.
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PMID:Attenuated adenosine-sensitivity and decreased adenosine-receptor number in adipocyte plasma membranes in human obesity. 165 38

1. Insulin increased basal 2-deoxyglucose uptake in isolated swine adipocytes by 75%. In the absence of insulin, isoproterenol did not inhibit basal 2-deoxyglucose transport. 2. Adenosine deaminase plus isoproterenol or theophylline alone reduced insulin effect by 10 and 40%, respectively. Isoproterenol alone or with 2-chloroadenosine did not inhibit insulin effect on glucose transport activity. 3. Insulin effect was inhibited by isoproterenol in the presence of theophylline but not in the presence of adenosine deaminase. 4. These results suggest that catecholamines do not counter-regulate basal and insulin-stimulated glucose transport in swine adipocytes.
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PMID:Effect of insulin and adrenergic agonists on glucose transport of porcine adipocytes. 198 40

We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4% or 14% of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were exposed to 10 microM-isoprenaline alone or with 5 micrograms of adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx. 50% (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14% of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucose-transport system.
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PMID:The relationship between insulin binding, insulin activation of insulin-receptor tyrosine kinase, and insulin stimulation of glucose uptake in isolated rat adipocytes. Effects of isoprenaline. 201 5

In rat adipocytes, the breakdown of phosphoinositides labelled by a 3 h incubation with [3H]inositol resulted in the accumulation of labelled inositol mono-, bis- and trisphosphates in the presence of oxytocin, vasotocin or vasopressin. Oxytocin at a concentration of 1 nM markedly increased phosphoinositide breakdown. Incubation of adipocytes both during the 3 h labelling and the 10 min breakdown period in a low adenosine medium (presence of adenosine deaminase) or high adenosine medium (presence of 0.1 microM N6-(phenylisopropyl)adenosine) (PIA) did not affect basal or ligand-stimulated phosphoinositide breakdown. The addition of 1 microM PIA only during the measurement of phosphoinositide breakdown variably stimulated basal breakdown but significantly potentiated that due to oxytocin. Isoproterenol similarly had little effect on basal but inhibited oxytocin stimulation of phosphoinositide breakdown. Insulin did not affect basal or ligand-stimulated phosphoinositide breakdown in the low or high adenosine medium. However, in adipocytes incubated in the absence of added adenosine deaminase or PIA, insulin stimulated basal accumulation of inositol phosphates by about 20% and inhibited that due to oxytocin by about 20%. There was no significant effect of insulin on the stimulation by vasopressin or vasotocin of phosphoinositide breakdown. These results indicate that, in adipocytes, phosphoinositide breakdown stimulated by oxytocin is enhanced by adenosine, inhibited by isoproterenol and, under some conditions is inhibited by insulin.
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PMID:Regulation of oxytocin-induced phosphoinositide breakdown in adipocytes by adenosine, isoproterenol and insulin. 255 83

The effect of neuropeptide Y (NPY) on cell contractions of ventricular myocytes isolated from the adult rat heart was investigated. Maximum changes in cell length (dL) during stimulated (0.5 Hz) contractions were determined in presence of the phosphodiesterase inhibitor Ro 20-1724 (0.5 mM) and adenosine deaminase (5 U/ml). Under these basal conditions NPY (10(-6) M) reduced dL by 39% of control. Isoproterenol (10(-6) M) increased dL by 105% of control; the EC50 was 2 x 10(-9) M. NPY reduced the increase in dL achieved by isoproterenol in a dose dependent manner. The IC50 value was 1 x 10(-9) M and NPY (10(-6) M) produced complete inhibition. In the absence of the phosphodiesterase inhibitor the IC50 was 4 x 10(-9) M. The EC50 of isoproterenol and IC50 of NPY producing accumulation of cAMP in myocytes (Millar et al. 1988) exceeded the respective values of dL by one order of magnitude. Prior treatment of the myocytes with pertussis toxin abolished the potency of NPY to antagonize the increase in dL by isoproterenol while not interfering with the response to the beta-agonist. These results demonstrate a negative inotropic effect of NPY on the ventricular myocardial cell. Complete abolition of the effect of NPY by pertussis toxin indicate that this effect is mediated by a sarcolemmal receptor for NPY linked to adenylate cyclase via an inhibitory guanine nucleotide binding protein.
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PMID:The negative inotropic effect of neuropeptide Y on the ventricular cardiomyocyte. 255 54

The effect of beta-adrenergic stimulation on insulin binding was studied in human fat cells in vitro. Isoproterenol rapidly (approximately 5 min) reduced insulin binding through a beta-adrenergic and dose-dependent mechanism. The reduced binding was enhanced by the addition of adenosine deaminase and was also elicited by the addition of dibutyryl cAMP. This effect was due to a decreased number of binding sites. The reduction was rapidly reversed by propranolol (t1/2 approximately 10 min) and other beta-adrenoreceptor blocking agents. Insulin binding was also measured in fat cells from 6 patients with a phaeochromocytoma. A significant negative correlation between tracer binding and the log value of total urinary catecholamine excretion was found (r = -0.821, p less than 0.05). Mean tracer insulin binding was reduced about 30% as compared to cells from 16 carefully matched control subjects. Decreased insulin binding was again mainly attributable to a decreased number of binding sites. Thus, beta-adrenergic stimulation, both in vitro and in vivo, leads to a decreased number of binding sites for insulin in human fat cells.
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PMID:Reduced insulin binding to human fat cells following beta-adrenergic stimulation--experimental evidence and studies in patients with a phaeochromocytoma. 286 56

Glucose transport as assessed by the uptake rate of 3-O-methylglucose was stimulated in isolated rat fat cells by preincubation with isoprenaline or orciprenaline. The effect was apparently mediated by beta 1-receptors, since (1) it was abolished by propranolol, (2) it closely paralleled the stimulation of lipolysis, and (3) isoprenaline was 10(2) times more potent that orciprenaline. Isoprenaline enhanced the effect of submaximal insulin concentrations as well as the basal transport rate but failed to increase the maximal effect of insulin. The stimulatory effect of isoprenaline was antagonized by adenosine deaminase which removes adenosine spontaneously released from the cells, and by bordetella toxin (IAP) which blocks the inhibitory coupling component of adenylate cyclase. Moreover, bordetella toxin uncovered an inhibitory effect of isoprenaline on insulin stimulated glucose transport. There was no apparent correlation between the effects on glucose transport and the response of cellular cyclic AMP levels to the agents investigated. It is suggested that a step in the coupling of beta-receptors and adenylate cyclase, but not total cellular cyclic AMP levels, may mediate stimulatory as well as inhibitory effects of catecholamines on glucose transport in the adipocyte.
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PMID:Dual effect of isoprenaline on glucose transport and response to insulin in isolated adipocytes. 298 32

The adenosine-sensitive cyclic AMP phosphodiesterase of rat adipocytes was found to reside in the same subcellular fraction as the enzyme sensitive to insulin. There were several similarities between the action of adenosine and that of insulin on the enzyme. The action of adenosine on the phosphodiesterase is probably like that of insulin, both being receptor-mediated, although different sites or different receptors could be involved. Adenosine analogues with intact ribose but a modified purine moiety elicited a response similar to that of adenosine. Added Ca2+ was also not a requirement for the action of adenosine. The action of adenosine was not synergistic with that of insulin, neither was adenosine essential for insulin action. Insulin stimulated the enzyme even at low cell concentrations and in the presence of adenosine deaminase. Adenosine, however, enhanced the effect of insulin, but only at insulin concentrations that produced submaximal effects. Thus the mechanisms of action could be similar or related. The time-course effect of a suboptimal concentration of insulin was transitory, like that of adenosine, and was influenced by the presence of adenosine, whereas that of a maximally effective concentration of insulin was sustained for at least 20 min and was not affected by the presence of adenosine. Isoprenaline enhanced phosphodiesterase activity stimulated by optimal concentrations of either adenosine or insulin, suggesting that their effects were mediated through different mechanisms of action.
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PMID:The action of adenosine in relation to that of insulin on the low-Km cyclic AMP phosphodiesterase in rat adipocytes. 298 6

The importance of endogenous myocardial adenosine in attenuating catecholamine-elicited contractile responses was investigated in perfused oxygenated rat hearts. Perfusion of the isolated hearts with adenosine deaminase potentiated the isoproterenol-induced increases of three contractile variables (left ventricular pressure development and rates of both left ventricular pressure development and relaxation). The peak (maximal, within 30 s) and maintained (after 1 min) increases of the contractile variables caused by 10(-8) M isoproterenol were enhanced by 15-22 and 31-43%, respectively. Adenosine deaminase appeared in epicardial surface transudates of similarly perfused hearts, indicating that the enzyme had entered the myocardial interstitial space. Isoproterenol alone elevated the release of adenosine into coronary effluents of isoproterenol-stimulated hearts, and adenosine deaminase prevented the release of the nucleoside. The higher the level of adenosine in the effluent, the greater the reduction of the peak contractile variables. Phenylisopropyladenosine at 10(-8) M prevented the adenosine deaminase potentiation of 10(-9) M isoproterenol-induced contractile responses. The adenosine analogue at 10(-6) M blocked completely the isoproterenol-produced increases in the contractile variables. These results suggest that endogenous adenosine prevents full mechanical responsiveness to beta-adrenoceptor stimulation in the oxygenated myocardium. In addition, the findings support the notion that adenosine serves as an important negative feedback modulator in the oxygenated heart.
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PMID:Endogenous adenosine inhibits catecholamine contractile responses in normoxic hearts. 374 Feb 98


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