Hormonal dose-response to an adenosine receptor agonist

Can J Physiol Pharmacol. 1994 Feb;72(2):113-6. doi: 10.1139/y94-018.


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.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Blood Glucose / drug effects
  • Corticosterone / blood
  • Dose-Response Relationship, Drug
  • Fatty Acids, Nonesterified / blood
  • Glucagon / blood
  • Insulin / blood
  • Male
  • Phenylisopropyladenosine / pharmacology*
  • Pituitary-Adrenal System / drug effects*
  • Rats
  • Rats, Wistar


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Phenylisopropyladenosine
  • Adrenocorticotropic Hormone
  • Glucagon
  • Corticosterone