Diuretic and saliuretic effects of 1,3-dipropyl-8-cyclopentylxanthine, a selective A1-adenosine receptor antagonist.
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.
Collis
M G
MG
ICI Pharmaceuticals, Mereside, Alderley Park Macclesfield, Cheshire, UK.
Shaw
G
G
Keddie
J R
JR
D000241:Adenosine / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D004573:Electrolytes / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D004573:Electrolytes; D011983:Receptors, Purinergic; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine