title: Increase in plasma free fatty acids and natriuresis by xanthines may reflect adenosine antagonism.
abstract: The hypothesis has been examined that adenosine is involved in the diuretic and free fatty acid (FFA) - releasing action of xanthines. The effects of theophylline (T), a potent adenosine antagonist, were compared with those of enprofylline (3-propyl xanthine, E), which exerts negligible antagonism of adenosine. Eight healthy male volunteers were given E 1.5 mg/kg, T 5.0 mg/kg or placebo 0.9% saline (P) intravenously in a double-blind, randomized, cross-over investigation. Blood samples were analyzed for E, T, catecholamines (CA: adrenaline, noradrenaline and dopamine), FFA, renin, glucose, glucagon and insulin, and urine was collected at 2-h intervals. T (plasma concentration 53 +/- 8 mumol/l) but not E (11 +/- 2 mumol/l) caused an increase in FFA from 0.42 to 0.86 mmol/l after 90 min. Without affecting the urinary excretion of potassium, T doubled natriuresis and the urine volume as compared to E and P. Neither T nor E had any effect on plasma CA, or on any other of the metabolic parameters studied. E, but not T, produced a small but statistically significant decrease in diastolic blood pressure (5 mmHg) and an increase in heart rate (3 beats/min). It is suggested that the difference between E and T in terms of stimulation of FFA-release and natriuresis may be related to their different ability to antagonize adenosine.
mesh_terms: D000241:Adenosine / Q000037:antagonists & inhibitors*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005934:Glucagon / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D012083:Renin / Q000097:blood; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014970:Xanthines; D005934:Glucagon; D013806:Theophylline; C034347:enprofylline; D012083:Renin; D000241:Adenosine