Stimulation of adenosine A3 receptors in cerebral ischemia. Neuronal death, recovery, or both?
The role of the adenosine A3 receptor continues to baffle, and, despite an increasing number of studies, the currently available data add to, rather than alleviate, the existing confusion. The reported effects of adenosine A3 receptor stimulation appear to depend on the pattern of drug administration (acute vs. chronic), dose, and type of the target tissue. Thus, while acute exposure to A3 receptor agonists protects against myocardial ischemia, it is severely damaging when these agents are given shortly prior to cerebral ischemia. Mast cells degranulate when their A3 receptors are stimulated. Degranulation of neutrophils is, on the other hand, impaired. While reduced production of reactive nitrogen species has been reported following activation of A3 receptors in collagen-induced arthritis, the process appears to be enhanced in cerebral ischemia. Indeed, immunocytochemical studies indicate that both pre- and postischemic treatment with A3 receptor antagonist dramatically reduces nitric oxide synthase in the affected hippocampus. Even more surprisingly, low doses of A3 receptor agonists seem to enhance astrocyte proliferation, while high doses induce their apoptosis. This review concentrates on the studies of cerebral A3 receptors and, based on the available evidence, discusses the possibility of adenosine A3 receptor serving as an integral element of the endogenous cerebral neuroprotective complex consisting of adenosine and its receptors.
von Lubitz
D K
DK
Department of Emergency Medicine, University of Michigan Health System, Ann Arbor 48109-0303, USA. dvlubitz@umich.edu
Ye
W
W
McClellan
J
J
Lin
R C
RC
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D051379:Mice; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine