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.
Adén
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Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. ulrika.aden@fyfa.ki.se
Leverin
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AL
Hagberg
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H
Fredholm
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BB
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology; D007457:Iodine Radioisotopes; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012007:Rectum; D013462:Sulfur Radioisotopes; D013997:Time Factors; D014970:Xanthines / Q000378:metabolism
D007457:Iodine Radioisotopes; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D013462:Sulfur Radioisotopes; D014970:Xanthines; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C106045:adenosine amine congener; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine