Hormonal dose-response to an adenosine receptor agonist.
The effect of various doses of i.p. injection of the adenosine receptor agonist (R)-phenylisopropyladenosine (R-PIA), ranging from nanomolar to micromolar concentrations, on plasma levels of free fatty acids, glucose, insulin, glucagon, ACTH, and corticosterone was examined in 200-g male rats. At the lowest dose of R-PIA (0.005 mumol/kg), a marked decrease in plasma insulin and free fatty acids was observed. This effect on free fatty acids persisted up to the highest concentration of R-PIA (50 mumol/kg). The insulin response showed a similar pattern except at the highest concentration, when the plasma levels were within normal ranges. A 100% increase in plasma glucose was found, but only with doses of 0.5 mumol/kg and above, suggesting an A2 receptor influence, possibly related to the elevation of plasma glucagon observed with the same doses of R-PIA. It has been shown that caffeine, an antagonist of adenosine, stimulates the pituitary--adrenal axis. Surprisingly, it was shown that R-PIA produces the same effect, as evidenced by the marked elevation of both plasma ACTH and corticosterone at concentrations of 0.5 mumol/kg and higher. It is suggested that this centrally mediated effect is due to a primary peripheral action.
LeBlanc
J
J
Department of Physiology, Faculty of Medicine, Laval University, Québec, Canada.
Soucy
J
J
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010660:Phenylisopropyladenosine; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D003345:Corticosterone