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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study tested the hypothesis that an A1 adenosine receptor capable of inhibiting adenylate cyclase activity is present in porcine coronary vascular smooth muscle cells. In the absence of blockade of the A2 adenosine receptor, the A1 adenosine receptor agonists phenylisopropyladenosine (PIA) and cyclopentyladenosine (CPA) (10(-9) M) failed to inhibit Gpp(NH)p stimulated adenylate cyclase activity. However, after blockade of the A2 adenosine receptor with 30 nM CGS 15943A, cyclopentyladenosine (10(-9) M) inhibited Gpp(NH)p stimulated adenylate cyclase activity by 27 +/- 3% (4.3 +/- 0.7, Mean +/- SEM; pmoles/min/mg vs 5.9 +/- 0.8, P less than .05). The data demonstrate that both A1 and A2 adenosine receptors are present in coronary vascular smooth muscle. The results indicate that adenosine may mediate both vasodilation and vasoconstriction in the coronary circulation via A2 and A1 adenosine receptors, respectively.
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PMID:Cultured vascular smooth muscle cells from porcine coronary artery possess A1 and A2 adenosine receptor activity. 234 87

Effects of chronic exposure of cultured atrial myocytes to R-N6-(2-phenylisopropyl)-adenosine (R-PIA) on the A1 adenosine receptor-mediated inhibition of adenylate cyclase activity and myocyte contractility were examined. Chronic exposure of atrial myocytes cultured from 14-day-old chick embryos to R-PIA desensitized the myocyte to the inhibitory effects of R-PIA on contractility and adenylate cyclase activity in a time- and dose-dependent manner. Desensitization of the negative inotropic response was only partial, whereas the adenosine receptor-mediated inhibition of adenylate cyclase activity was almost completely absent after 24 hours of R-PIA (1 microM) exposure. Furthermore, the contractile response to R-PIA desensitized more slowly than the desensitization of A1 adenosine receptor-mediated inhibition of adenylate cyclase (t1/2 = 11.4 +/- 0.7 hours versus 7.5 +/- 1 hours, mean +/- SEM, n = 12 and 6, respectively). Thus, the two A1 adenosine receptor-linked functional responses desensitized differently in response to chronic exposure of the myocyte to R-PIA. Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3-dipropylxanthine [( 3H]CPX) in membranes from myocytes preexposed to R-PIA demonstrated a time-dependent decrease in receptor density without any change in the affinity for the antagonist radioligand. Computer analyses of agonist competition with [3H]CPX binding in membranes from control and R-PIA-treated myocytes revealed a conversion of the high-affinity A1 adenosine receptor to a low-affinity form such that after 24 hours of 1 microM R-PIA exposure, all of the receptors were in a low-affinity form.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential desensitization of A1 adenosine receptor-mediated inhibition of cardiac myocyte contractility and adenylate cyclase activity. Relation to the regulation of receptor affinity and density. 237 79

Injections of N6-(phenylisopropyl)adenosine, a nonmetabolizable adenosine A1 receptor agonist, desensitized rat adipocytes to the drug in 20 h. Lipolysis stimulated by 2 mumol/l DL-isoproterenol was inhibited markedly less by N6-(phenylisopropyl)adenosine in adipocytes isolated from treated than control animals (P less than 0.01). Glucose uptake was more responsive to N6-(phenylisopropyl)adenosine in adipocytes from control than treated animals (P less than 0.02). Adenosine content was the same in adipose tissue of control and treated animals. The number of adenosine binding sites was not significantly lower in treated compared with control animals (1580 +/- 279 and 1988 +/- 575 fmol/mg protein; mean +/- SEM). There was no change in receptor affinity (Kd = 10 nmol/l in both groups). There was no decrease in the amounts of the inhibitory guanine nucleotide binding protein (Gi) alpha subunits as studied by pertussis toxin catalyzed ADP-ribosylation. It is concluded that desensitization to N6-(phenylisopropyl)adenosine can be observed without changes in the adenosine receptor status or decrease in the amount of inhibitory guanine nucleotide binding protein and that adipose tissue adenosine content is not changed by the agonist treatment.
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PMID:Rat adipose tissue adenosine sensitivity and adenosine content after subcutaneous administration of N6-(phenylisopropyl)adenosine. 292 38

This study was designed to examine: (a) the effects of adenosine and its analogues on renin release in the absence of tubules, glomeruli, and macula densa, and (b) whether adenosine may be involved in a macula densa-mediated renin release mechanism. Rabbit afferent arterioles (Af) alone and afferent arterioles with macula densa attached (Af + MD) were microdissected and incubated for two consecutive 30-min periods. Hourly renin release rate from a single arteriole (or an arteriole with macula densa) was calculated and expressed as ng AI X h-1 X Af-1 (or Af + MD-1)/h (where AI is angiotensin I). Basal renin release rate from Af was 0.69 +/- 0.09 ng AI X h-1 X Af-1/h (means +/- SEM, n = 16) and remained stable for 60 min. Basal renin release rate from Af + MD was 0.20 +/- 0.04 ng AI X h-1 X Af + MD-1/h (n = 6), which was significantly lower (P less than 0.0025) than that from Af. When adenosine (0.1 microM) was added to Af, renin release decreased from 0.72 +/- 0.16 to 0.24 +/- 0.04 ng AI X h-1 X Af-1/h (P less than 0.025; n = 9). However, when adenosine was added to Af + MD, no significant change in renin release was observed. N6-cyclohexyl adenosine (an A1 adenosine receptor agonist) at 0.1 microM decreased renin release from Af from 0.69 +/- 0.14 to 0.39 +/- 0.12 ng AI X h-1 X Af-1/h (n = 5, P less than 0.05). However, 5'-N-ethylcarboxamide adenosine (an A2 adenosine receptor agonist) either at 0.1 microM or at 10 microM had no effect. Theophylline, at a concentration (10 microM) that does not block phosphodiesterase but does block adenosine receptors, increased renin release from Af + MD from 0.21 +/- 0.03 to 0.46 +/- 0.08 ng AI X h-1 X Af + MD-1/h (P less than 0.05; n = 8). The results are consistent with the hypotheses that adenosine decreases renin release via the activation of A1 adenosine receptors, and that adenosine may be an inhibitory signal from the macula densa to juxtaglomerular cells.
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PMID:Possible role of adenosine in the macula densa mechanism of renin release in rabbits. 299 77

We previously reported that the adenosine receptor agonist N6-phenylisopropyladenosine (R-PIA) inhibits adenylyl cyclase in detergent-permeabilized embryonic chick ventricular myocytes in the presence of the adrenergic receptor agonist, isoproterenol (Ma and Green 1992). The slope of the dose response curve of this inhibition is very shallow (nH 0.3-0.4). The present studies on detergent-permeabilized chick myocytes evaluate the mechanisms underlying this shallow inhibition curve. We find that in contrast to R-PIA, two additional adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and 2-chloro-N6-cyclopentyladenosine (CCPA), inhibit cardiac adenylyl cyclase activity in a monophasic, dose-dependent manner (nH approximately 1). Two A1 adenosine receptor antagonists, 8-cyclopentyl-1,3,-dipropylxanthine (CPX) and 3-(4-amino)phenethyl-1-propyl-8-cyclopentylxanthine (BW-A884U) affect the R-PIA responses differently. BW-A884U shifts the R-PIA dose response curve to the right in a parallel fashion while CPX both shifts the R-PIA response curve and increases its steepness. Cardiac A1 adenosine receptors were further characterized using one antagonist ([3H]CPX) and two agonist ([3H]R-PIA and [3H]CCPA) radioligands. [3H]CPX binds to the adenosine receptors in detergent-permeabilized ventricular myocytes with a Kd value of 3.3 +/- 0.2 nM and a BMAX value of 30.1 +/- 2.4 fmol/mg protein (means +/- SEM; N = 4). [3H]R-PIA detects more sites than [3H]CCPA (22.8 +/- 4.0 and 8.3 +/- 1.3 fmol/mg protein, respectively; GTP-free conditions). CPA and CCPA inhibit [3H]R-PIA binding in a shallow, dose-dependent manner (nH approximately 0.4), while R-PIA and CPA inhibit [3H]CCPA binding with a nH approximately 1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine receptor-mediated inhibition of cardiac adenylyl cyclase activity may involve multiple receptor subtypes. 813 4

The adenosine A1 receptor antagonist (FR113453) prevents glycerol- but not mercury-induced acute renal failure. To clarify this mechanism, adenosine concentration in the renal vein was measured serially. Plasma adenosine in the renal vein increased from the preinjection value of 120.6 +/- 15.4 (mean +/- SEM) pmol/ml to 426.9 +/- 107.5, 407.0 +/- 70.1 and 283.9 +/- 22.9 pmol/ml at 1, 5 and 60 min after intramuscular injection of 10 mg/kg of 50% glycerol into Sprague-Dawley rats. On the other hand, intramuscular vehicle (0.9% NaCl) injection and subcutaneous administration of 10 mg/kg of HgCl2 did not change or caused mild elevation of adenosine concentration in the renal vein. Furthermore, simultaneous blood collection from the carotid artery, renal vein and inferior vena cava revealed a greater increase in adenosine concentration in the inferior vena cava than in the artery or renal vein. These findings were not affected by the administration of FR113453 or vehicle (methylcellulose). The increase in adenosine in the inferior vena cava was derived from the release from the acutely damaged muscles due to glycerol injection. These findings suggest that the effect of adenosine A1 antagonist to prevent glycerol-induced acute renal failure is due to the inhibition of adenosine A1 receptor in the kidneys during the release of adenosine through the inferior vena cava. Therefore, the release of adenosine from the muscle and hemolysis plays an important role to induce acute renal failure in the glycerol-injected rat.
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PMID:Changes of adenosine levels in the carotid artery, renal vein and inferior vena cava after glycerol or mercury injection in the rat. 836 87

In this study we investigated the relationship between the pharmacokinetics and the cardiovascular and electroencephalogram (EEG) effects of three adenosine agonists with differing lipophilicity. Conscious normotensive rats received either 600 microg/kg N6-(p-sulphophenyl) adenosine (SPA), 200 microg/kg N6-cyclopentyladenosine (CPA) or 600 microg/kg 1-deaza-2-chloro-N6-cyclopentyladenosine (DCCA) in a 5-min intravenous infusion. Changes in haemodynamics and EEG were monitored in conjunction with arterial blood sampling to determine blood concentrations of the compounds. The three adenosine agonists showed large differences in pharmacokinetic properties, resulting in terminal half-lives of 66 +/- 10, 8.2 +/- 0.4 and 24 +/- 1 min (mean +/- SEM) for SPA, CPA, and DCCA respectively. SPA had a significantly lower blood clearance relative to CPA and DCCA, whereas DCCA had the largest volume of distribution and degree of plasma protein binding. The relationship between concentration and heart rate could be described adequately by the sigmoidal Emax model. For SPA, CPA, and DCCA the EC50 values based on free drug concentrations were 423 +/- 92, 1.8 +/- 0.4 and 9.5 +/- 1.1 nM respectively. These in vivo values correlated closely with the affinity of the compounds for the adenosine A1 receptor as determined in radioligand binding studies, with corresponding Ki values of 1410 +/- 220, 4.7 +/- 0.6 and 102 +/- 74 nM (mean +/- SEM) respectively. In the EEG, only CPA produced a small decrease in the amplitude of beta waves. This study demonstrates that the three adenosine analogues have large differences in pharmacokinetics, which complicates comparison of their cardiovascular and central responses simply on the basis of dose. The application of an integrated PK/PD approach permits estimates of potency and activity which are independent of underlying dose and pharmacokinetics.
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PMID:Time course of action of three adenosine A1 receptor agonists with differing lipophilicity in rats: comparison of pharmacokinetic, haemodynamic and EEG effects. 945 70