Adenosine Receptor Subtypes: Binding Studies

Bruns, Robert F.; Lu, Guowei; Pugsley, Thomas A.

doi:10.1007/978-3-642-45619-0_6

Cited by 70 publications

(58 citation statements)

References 34 publications

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“…Caffeine is an antagonist of both A 1 and A 2 adenosine receptors (26). There is controversy about the mechanism that mediates the memory-improving effect of caffeine.…”

Section: Discussionmentioning

confidence: 99%

Effects of caffeine on learning and memory in rats tested in the Morris water maze

Angelucci

Cesário

Hiroi

et al. 2002

Braz J Med Biol Res

116

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We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. Groups of 12 adult male Wistar rats receiving caffeine (0.3-30 mg/kg, ip, in 0.1 ml/100 g body weight) administered 30 min before training, immediately after training, or 30 min before the test session were tested in the spatial version of the Morris water maze task. Post-training administration of caffeine improved memory retention at the doses of 0.3-10 mg/kg (the rats swam up to 600 cm less to find the platform in the test session, P£0.05) but not at the dose of 30 mg/kg. Pre-test caffeine administration also caused a small increase in memory retrieval (the escape path of the rats was up to 500 cm shorter, P£0.05). In contrast, pre-training caffeine administration did not alter the performance of the animals either in the training or in the test session. These data provide evidence that caffeine improves memory retention but not memory acquisition, explaining some discrepancies among reports in the literature. Correspondence

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“…Caffeine is an antagonist of both A 1 and A 2 adenosine receptors (26). There is controversy about the mechanism that mediates the memory-improving effect of caffeine.…”

Section: Discussionmentioning

confidence: 99%

Effects of caffeine on learning and memory in rats tested in the Morris water maze

Angelucci

Cesário

Hiroi

et al. 2002

Braz J Med Biol Res

116

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“…This isothiocyanate was shown by thin-layer chromatography to be converted completely to the ethylenediamine adduct (8, Scheme I) under these conditions. The K i values against binding of 18 Those xanthine derivatives evaluated (Table IV) were generally A 1 -selective, in the range of 30-to 150-fold. Aryl isothiocyanate derivatives of adenosine, 45 and 46, were 200-to 600-fold A 1 selective.…”

Section: Biologymentioning

confidence: 94%

Electrophilic derivatives of purines as irreversible inhibitors of A1 adenosine receptors

Jacobson¹,

Barone²,

Kammula³

et al. 1989

J. Med. Chem.

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Functionalized congeners derived from 1,3-dipropyl-8-phenylxanthine and from N 6 -phenyladenosine were derivatized to contain electrophilic groups (isothiocyanate, Nhydroxysuccinimide ester, maleimide, sulfonyl chloride, or α-haloacyl group) capable of reaction with nucleophiles on biopolymers. The goal was to inhibit chemically the A 1 adenosine receptor by using reactive agonist and antagonist ligands. Some of the electrophilic derivatives were synthesized through acylation of amine-functionalized congeners using hetero-or homobifunctional reagents available for protein cross-linking. The affinity for A 1 adenosine receptors was evaluated in competitive binding assays by using rat and bovine brain membranes. Several xanthine and adenosine thiourea derivatives prepared from 1,3-and l,4-phenylene diisothiocyanate (DITC) were potent irreversible inhibitors of adenosine receptors. Derivatives of m-DITC, at concentrations between 10 and 500 nM, irreversibly eliminated binding at 90% of the A 1 -receptor sites. Receptor affinity of both xanthine and adenosine derivatives containing distal phenylthiourea substituents was diminished by electron-donating groups on the ring.Adenosine modulates a variety of physiological functions. 1 It acts as an inhibitor of neuronal firing and the release of neurotransmitters, 1b an inhibitor of platelet aggregation, 1c a cardiac depressant and a vasodilator, 1d a vasoconstrictor 1e (e.g., in the renal afferent arterioles and in the skin), and an immunosuppressant. 1f Most of the physiological effects of adenosine result from binding to discrete membrane-bound adenosine receptors of the A 1 or A 2 subtypes. 1g The xanthine drugs caffeine and theophylline, and many synthetic analogues, 2 act as competitive antagonists at adenosine receptors.Alkylating or acylating ligands that form a stable covalent bond with a receptor have been synthesized for a number of receptors, including opiate, 3,4 phencyclidine, 5 adrenergic, 6 and benzodiazepine receptors. 7 The utility of such chemically irreversibly bound ligands for characterizing receptors in membranes and in physiological systems, 4,5 and in receptor identification, 8 has been demonstrated. For adenosine receptors, only photoaffinity labels 1g,9 have hitherto been described. We now report a set of reactive adenosine receptor ligands, derived from agonist 10 and antagonist 11 functionalized congeners. These ligands contain electrophilic acylating and alkylating groups capable of reaction with nucleophilic residues in proximity to the adenosine receptor binding site.

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“…The supernatant was lyophilized and resolubilized in water. Cyclic AMP levels were quantified by radioimmunoassays as described previously (Brooker et al, 1979;Van Sande and Dumont, 1973 Binding studies Membranes from thyroid and brain tissues were prepared as a crude 40 000 g pellet as described (Bruns et al, 1986). Before storage, membranes were incubated for 30 min at 37°C in the presence of adenosine deaminase (Boehringer; 2.5 U/ml) and measurement of protein content was carried out by using the Lowry assay as modified by Peterson (1977).…”

Section: Methodsmentioning

confidence: 99%

“…[3H]CGS21680 (48.1 Ci/mmol; NEN) as tracer and 0.2 U/mi adenosine deaminase (Bruns et al, 1986). Non-specific binding was determined in the presence of 100 MM N6-cyclopentyladenosine (CPA; Sigma) as unlabelled competitor.…”

Section: Methodsmentioning

confidence: 99%

“…Non-specific binding was determined in the presence of 100 MM N6-cyclopentyladenosine (CPA; Sigma) as unlabelled competitor. After 90 min at room temperature, membranes were rapidly vacuum filtered through GF-C membranes (Millipore) and washed three times with ice-cold 50 mM Tris-HCI buffer (Bruns et al, 1986 Tissues for electron microscopy were collected under anesthesia, fixed in 2% glutaraldehdye in 100 mM phosphate buffer, pH 7.2 and postfixed in 2 % O004 in the same buffer. 60 nm thick sections were cut after Epon embedding.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism.

et al. 1992

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Adenosine Receptor Subtypes: Binding Studies

Cited by 70 publications

References 34 publications

Effects of caffeine on learning and memory in rats tested in the Morris water maze

Effects of caffeine on learning and memory in rats tested in the Morris water maze

Electrophilic derivatives of purines as irreversible inhibitors of A1 adenosine receptors

Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism.

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