Protective effect of cyclohexyladenosine on adenosine A1-receptors, guanine nucleotide and forskolin binding sites following transient brain ischemia: a quantitative autoradiographic study.
The effects of an i.p. administration of cyclohexyladenosine (CHA) have been examined upon ischemic brain damage in gerbils. Ischemia was induced for 20 min by occlusion of both carotid arteries, and CHA was administered 5 min after recirculation at a dose of 2 mg/kg. Animals were sacrificed either 1, 3 or 6 days after ischemia and their brains were used for examination of cell morphology and quantitative autoradiography. In animals subject to ischemia, the deterioration of the laminar organization of the hippocampus was associated with a significant decrease in adenosine A1-receptors (labeled with [3H]CHA), G-protein (labeled with [3H]forskolin). The treatment with CHA considerably improved the morphological preservation of cells in the CA1 region of the hippocampus and prevented the reduction in the specific binding of all radioligands. Adenosine, its analogues and other substances modulating adenosine receptors may thus provide new therapeutic approaches to the treatment of ischemia-induced brain injury.
Daval
J L
JL
National Institute of Mental Health, Bethesda, MD 20892.
Von Lubitz
D K
DK
Deckert
J
J
Redmond
D J
DJ
Marangos
P J
PJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*
D011983:Receptors, Purinergic; D005576:Colforsin; C027513:N(6)-cyclohexyladenosine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000241:Adenosine