Adenosine A(1) receptor agonism in the immature rat brain and heart

Eur J Pharmacol. 2001 Aug 31;426(3):185-92. doi: 10.1016/s0014-2999(01)01220-1.


We examined if the adenosine A(1) receptor agonist adenosine amine congener (ADAC, 100 microg/kg i.p.) is neuroprotective in 7-day-old rats subjected to hypoxic ischemia. Brain damage, evaluated as weight deficit and gross morphology, was not affected by ADAC treatment. Nonetheless, ADAC (100 microg/kg i.p.) reduced heart rate by 44% (p<0.0001), indicating that the dose given was pharmacologically active. Adenosine A(1) receptors were determined by [(3)H] 1,3-dipropyl-8-cyclopentylxanthine (DPCPX)-binding and levels were 23% of the adult levels. GTP did not affect [(3)H] DPCPX-binding in the cerebral cortex at postnatal day 7 whereas there was strong enhancement of [(3)H] DPCPX-binding in the heart. This suggested a poor G-protein coupling at postnatal day 7 in the brain, which also was confirmed using GTP [gamma-(35)S]-binding in the presence of an adenosine A(1) receptor agonist. Thus, the lack of a neuroprotective effect of ADAC may be explained by the fact that adenosine A(1) receptors are not part of a functional unit in the 7-day-old rat brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Animals
  • Animals, Newborn
  • Binding, Competitive
  • Body Temperature / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / physiopathology
  • Dose-Response Relationship, Drug
  • Female
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Rate / drug effects
  • Hypoxia / physiopathology
  • Iodine Radioisotopes
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Purinergic P1 Receptor Agonists
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P1 / physiology*
  • Rectum
  • Sulfur Radioisotopes
  • Time Factors
  • Xanthines / metabolism


  • Iodine Radioisotopes
  • Purinergic P1 Receptor Agonists
  • Receptors, Purinergic P1
  • Sulfur Radioisotopes
  • Xanthines
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • adenosine amine congener
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Adenosine