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

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.