Adenosine A3 receptor stimulation and cerebral ischemia.
Chronic treatment with the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA) administered prior to either 10 or 20 min forebrain ischemia in gerbils resulted in improved postischemic cerebral blood circulation, survival, and neuronal preservation. Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and extensive neuronal destruction in the hippocampus were seen when IB-MECA was given acutely. Neither adenosine A1 nor A2 receptors are involved in these actions. The data indicate that stimulation of adenosine A3 receptors may play an important role in the development of ischemic damage, and that adenosine A3 receptors may offer a new target for therapeutic interventions.
Von Lubitz
D K
DK
NIH/NIDDK, Laboratory of Bioorganic Chemistry, Bethesda, MD 20892.
Lin
R C
RC
Popik
P
P
Carter
M F
MF
Jacobson
K A
KA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D005849:Gerbillinae; D009474:Neurons / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D000241:Adenosine