Diuretic and saliuretic effects of 1,3-dipropyl-8-cyclopentylxanthine, a selective A1-adenosine receptor antagonist

Author:

Collis M G1,Shaw G1,Keddie J R1

Affiliation:

1. ICI Pharmaceuticals, Mereside, Alderley Park Macclesfield, Cheshire SK10 4TG, UK

Abstract

Abstract We have previously shown that 8-phenyltheophylline (8-PT), a non-selective antagonist at adenosine A1-and A2-receptors, has a diuretic effect. In this study, the diuretic and adenosine antagonist effects of the A1-receptor selective compound 1,3-dipropyl-8-cyclopentylxanthine (CPX) have been examined in the conscious rat. CPX (0.1 and 0.3 mg kg−1 i.v.) significantly attenuated bradycardic but not hypotensive responses evoked by adenosine. In contrast, 8-PT (3 mg kg−1 i.v.) significantly antagonized both adenosine-induced bradycardia and hypotension. CPX (0.1 and 0.3 mg kg−1 i.v.) evoked a dose-related diuretic and saliuretic response in the conscious rat. These results indicate that the diuretic effects of adenosine antagonists are associated with blockade of the A1-receptor sub-type.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference14 articles.

1. Adenosine A1 receptor mediated inhibition of nerve stimulation induced contractions of the rabbit portal vein;Brown;Eur. J. Pharmacol.,1983

2. Adenosine relaxes the aorta by interacting with an A2 receptor and an intracellular site;Collis;Ibid.,1983

3. An investigation of the negative chronotropic effect of adenosine on the guinea-pig atrium;Collis;Br. J. Pharmacol.,1984

4. The adenosine receptor antagonist, 8-phenyltheophylline, causes diuresis and saliuresis in the rat;Collis;J. Pharm. Pharmacol.,1986

5. Apparent affinity of 1,3-dipropyl-8-cyclopentylxanthine for adenosine A1 and A2 receptors in isolated tissues from guinea-pigs;Collis;Br. J. Pharmacol.,1989

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