Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.17 (adenosine deaminase)
 5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative autoradiography was used to investigate the effects of Mg2+ on agonist and antagonist binding to A1 receptors in rat striatum. A1 receptors were labelled with the selective agonist N6-[3H]cyclohexyladenosine ([3H]CHA) or the selective antagonist 1,3-[3H]dipropyl-8-cyclopentylxanthine ([3H]DPCPX). Mg2+ had no significant effect on equilibrium binding constants for [3H]CHA [control: KD (95% confidence interval) of 0.34 (0.15-0.80) nM and Bmax of 267 +/- 8 fmol/mg of gray matter; with 10 mM Mg2+: KD of 0.8 (0.13-4.9) nM and Bmax of 313 +/- 8.9 fmol/mg of gray matter] or [3H]DPCPX [control: KD of 0.54 (0.30-0.99) nM and Bmax of 256 +/- 2.3 fmol/mg of gray matter; with 10 mM Mg2+: KD of 1.54 (0.2-11.0) nM and Bmax of 269 +/- 35.7 fmol/mg of gray matter]. In contrast, Mg2+ slowed the apparent association rate for both ligands; this was observed as a shift from a one-component to a two-component model for [3H]DPCPX. Mg2+ also affected the dissociation rates of both ligands; for [3H]CHA, dissociation in the presence of Mg2+ was not detected. Mg2+ produced a concentration-dependent inhibition of [3H]CHA binding only prior to equilibrium. HPLC was performed on untreated sections, sections preincubated with adenosine deaminase (ADA), and sections preincubated with ADA and incubated with ADA in the absence or presence of Mg2+. Adenosine was found in measurable quantities under all conditions, and the concentration was not influenced by Mg2+ or by the inclusion of GTP in the preincubation medium. From these data, we conclude the following: (a) adenosine is present and may be produced continuously in brain sections; (b) ADA is not capable of completely eliminating the produced adenosine; (c) Mg2+ apparently does not influence adenosine production or elimination; (d) A1 receptor-guanine nucleotide binding protein coupling is maximal in this preparation; and (e) Mg2+ decreases the dissociation rate of bound endogenous adenosine from A1 receptors, thus limiting the access of [3H]CHA and [3H]DPCPX to the receptors. Thus, enhancement of endogenous adenosine binding to A1 receptors by Mg2+ is a complicating factor in receptor autoradiography and may be so in other preparations as well.
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PMID:Magnesium-dependent enhancement of endogenous agonist binding to A1 adenosine receptors: a complicating factor in quantitative autoradiography. 173 1

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

Adenosine attenuates beta-adrenergic receptor mediated activation of adenylate cyclase in myocardial membranes via adenosine Ri receptors. The effects of adenosine analogs on the binding characteristics of beta-adrenergic receptors were examined in the present study utilizing rat ventricular membranes treated with adenosine deaminase. In 125I-cyanopindolol/isoproterenol competitive binding experiments phenylisopropyladenosine (PIA) significantly increased the IC50 for isoproterenol from 48 +/- 6 nM to 140 +/- 48 nM and steepened the slope of the competition curves from -0.56 +/- 0.03 to -0.90 +/- 0.21. Computer analysis of these curves indicated that binding of isoproterenol to the high affinity state of the beta-adrenergic receptor was eliminated in the presence of PIA. PIA had no effects in the presence of GPP(NH)P. 2-chloroadenosine, a less specific Ri agonist, caused smaller increases in IC50 and slope, without significantly affecting high affinity binding. 2',5'-dideoxyadenosine, a P-site agonist, had no significant effects on isoproterenol binding. During the time course of the competitive binding experiments the membranes displayed isoproterenol-sensitive adenylate cyclase activity in the absence of added GTP. These data suggest that adenosine attenuates catecholamine-induced activation of adenylate cyclase via Ri receptors by decreasing the ability of beta-adrenergic agonists to promote the formation of a high affinity complex composed of the agonist, receptor and stimulatory guanine nucleotide binding protein.
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PMID:The adenosine Ri agonist, phenylisopropyladenosine, reduces high affinity isoproterenol binding to the beta-adrenergic receptor of rat myocardial membranes. 284 21