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

Abstract

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.

• Authors: U Adén, A L Leverin, H Hagberg, B B Fredholm
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 426 Issue 3 Pg. 185-92 (Aug 31 2001) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11527543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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