Adenosine receptors: pharmacology, structure-activity relationships, and therapeutic potential

Jacobson, Kenneth A.; Galen, P. J. M. van; Williams, Michael

doi:10.1021/jm00081a001

Cited by 464 publications

(422 citation statements)

References 134 publications

(190 reference statements)

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“…The most potent compounds in the fluorescence assay, NECA and DPMA, are among the most potent agonists known at A 2a -adenosine receptors. 2-CADO, CHA, and R-PIA displayed an intermediate affinity, consistent with the A 1 selectivity of these N 6 -substituted adenosine derivatives [19]. CV 1808, although slightly A 2a -adenosine receptor selective [23], was of a submicromolar affinity in the fluorescence assay and in agreement with the K i value determined by radioligand binding.…”

Section: Discussionsupporting

confidence: 63%

“…4, Table I). The rank order of potency found for the inhibitors was that expected for A 2a -adenosine receptors [19]. Moreover, an excellent correlation (r = 0.97, P = 0.0003) was obtained between the potencies of a series of A 2a -adenosine receptor ligands as inhibitors of FITC-APEC and [ 3 H]NECA binding [23] (Fig.…”

Section: Discussionmentioning

confidence: 70%

“…Displacement of FITC-APEC by purine derivatives of known ȧtffinity at A 2a -adenosine receptors indicated a characteristic rank order of potency. Representative curves for inhibition of FITC-APEC (50 nM) binding by NECA, DPMA, 2-CADO, and CV 1808 (adenosine derivatives displaying a high affinity and/or moderate selectivity at A 2a -adenosine receptors [19]) are illustrated in Fig. 4.…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, a fluorescent ligand having a high affinity for A 2a -adeonsine receptors [12][13][14][15]19] [20].…”

Section: Introductionmentioning

confidence: 99%

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2-[2-[4-[2-[2-[1,3-Dihydro-1,1-bis(4-hydroxyphenyl)-3-oxo-5-isobenzofuranthioureidyl]ethylaminocarbonyl]ethyl]phenyl] ethylamino]-5?-N-ethylcarboxamidoadenosine (FITC-APEC): A fluorescent ligand for A2a-adenosine receptors

1992

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 70%

Section: Resultsmentioning

confidence: 99%

“…In the present study, a fluorescent ligand having a high affinity for A 2a -adeonsine receptors [12][13][14][15]19] [20].…”

Section: Introductionmentioning

confidence: 99%

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2-[2-[4-[2-[2-[1,3-Dihydro-1,1-bis(4-hydroxyphenyl)-3-oxo-5-isobenzofuranthioureidyl]ethylaminocarbonyl]ethyl]phenyl] ethylamino]-5?-N-ethylcarboxamidoadenosine (FITC-APEC): A fluorescent ligand for A2a-adenosine receptors

1992

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“…subtypes [1], based upon their properties of activating (A 2 ) or inhibiting (A 1 ) adenylate cyclase activity, and according to the order of agonist potency [2,3].…”

mentioning

confidence: 99%

Characterization of adenosine receptors in intact cultured heart cells

El-Ani

Shainberg

1994

Biochemical Pharmacology

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Adenosine receptors were studied on heart cells grown in cultures by the radioligand binding technique. We used the hydrophilic A 1 adenosine receptor radioligand [ 3 H]-8-cyclopentyl-1,3-dipropylxanthine ([ 3 H]CPX), to monitor the level of the receptors on intact cardiocytes. The binding showed high affinity (K d = 0.13 nM) and the number of [ 3 H]CPX binding sites (B max ) was 23.1 fmol/dish (21 fmol/mg protein). The K i of the agonists R-N 6 -(2-phenylisopropyl)-adenosine (R-PIA) and S-N 6 -(2-phenylisopropyl)-adenosine (S-PIA), and of the antagonists CPX and theophylline were 3.57, 49.0, 1.63 and 4880 nM, respectively. The number of adenosine receptors was very low during the first days in cultures (5 fmol/dish) and increased gradually until it reached a plateau on days 8-10. Treatment with norepinephrine or isoproterenol which accelerated the rate of contractions, induced up regulation of the receptors. B max increased 2-3-fold by application of norepinephrine for 4 days, while receptor affinity to the radioligand was unaffected. Lactate dehydrogenase (LDH) and creatine kinase (CK) activity increased only by 22 and 38%, respectively. Similarly, 3 days treatment with triiodothyronine (T 3 , 10 −8 M), which also accelerated heart rate, increased the number of adenosine receptors by 56% without a significant change in the affinity of the receptors to [ 3 H]CPX. Carbamylcholine (5 × 10 −6 M), which reduced the rate of heart contractions, caused 26% down regulation while the affinity of the receptors remained unchanged. It is concluded that there is a linkage between the rate of cardiac contractions and the level of adenosine receptors. Thus, the level of adenosine receptors may respond to drug-induced chronic changes in cardiac contractile activity so as to restore conditions to normal (basal) contractions. KeywordsCPX; heart-rate; norepinephrine; thyroid hormones Adenosine modulates a variety of physiological functions in the heart. These actions are mediated by cell surface adenosine receptors, which can be classified into A 1 and A 2 † Corresponding author. Tel. (972)3-5318265; FAX (972)3-5351824. In conditions of stress like hypoxia or ischemia, the concentration of adenosine in the extracellular fluid rises dramatically, mainly through the breakdown of ATP [4]. In these conditions adenosine has therapeutic and protective effects on the heart [5,6]. Adenosine causes negative chronotropic, dromotropic and ionotropic effects on the cardiac tissue via A 1 receptors [7,8]. Adenosine also acts as a coronary vasodilator via A 2 receptors [9]. These effects of adenosine occur also without prior catecholamine treatment [10]. Stimulation that enhances the cAMP content (catecholamines, forskolin, amrinone), makes the heart more sensitive to adenosine [11][12][13][14]. In addition, adenosine causes hyperpolarization by activation of K + channels [15] via G proteins [16, 17]. These K + channels are the same channels that are stimulated by acetylcholine in the cardiac tissue [18][19][20]. HHS Public AccessChron...

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Effects of ATP and derivatives on neuropile glial cells of the leech central nervous system

Müller

Henrich

Klockenhoff

et al. 2000

Glia

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Adenosine receptors: pharmacology, structure-activity relationships, and therapeutic potential

Abstract: Note Added in Proof: Glaxo has recently reported 170 on GR 79236, an orally active A 1 -receptor selective agonist targeted for the treatment of type II diabetes. The Pzy receptor has been expressed from guinea pig brain mRNA.

Cited by 464 publications

References 134 publications

2-[2-[4-[2-[2-[1,3-Dihydro-1,1-bis(4-hydroxyphenyl)-3-oxo-5-isobenzofuranthioureidyl]ethylaminocarbonyl]ethyl]phenyl] ethylamino]-5?-N-ethylcarboxamidoadenosine (FITC-APEC): A fluorescent ligand for A2a-adenosine receptors

2-[2-[4-[2-[2-[1,3-Dihydro-1,1-bis(4-hydroxyphenyl)-3-oxo-5-isobenzofuranthioureidyl]ethylaminocarbonyl]ethyl]phenyl] ethylamino]-5?-N-ethylcarboxamidoadenosine (FITC-APEC): A fluorescent ligand for A2a-adenosine receptors

Characterization of adenosine receptors in intact cultured heart cells

Effects of ATP and derivatives on neuropile glial cells of the leech central nervous system

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