Adenosine A1 receptor activation preferentially protects cultured cerebellar neurons versus astrocytes against hypoxia-induced death.
Administration of adenosine A1 receptor agonists in vivo is neuroprotective in various stroke models. Experiments using either mixed cultures of neurons and astrocytes or brain slices, in which several cell types are present, have demonstrated that activation of A1 receptors also id protective against hypoxia and/or hypoglycemia in vitro. In this study, we have examined the effect of the A1 agonist cyclopentyladenosine (CPA) on cellular damage, measured by efflux of lactate dehydrogenase (LDH), in highly enriched primary cultures of either neurons of astrocytes exposed to different metabolic insults. CPA reduced neuronal LDH release induced by a combination of hypoxia and substrate deprivation ("simulated ischemia"; IC50 = 28 nM) of by hypoxia alone (IC50 = 170 nM). In contrast, CPA had no effect on neuronal damage induced by substrate deprivation alone, not did it affect ischemic death to astrocytes. The neuroprotective effect of CPA during simulated ischemia and hypoxia were reversed by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). These data demonstrate that activation of an adenosine A1 receptor on neurons, but not astrocytes, is protective against cellular damage of death induced specifically by hypoxia as opposed to other metabolic insults such as hypoglycemia.
Logan
M
M
Department of Physiology, University of Saskatchewan, Saskatoon, Canada.
Sweeney
M I
MI
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007003:Hypoglycemia / Q000201:enzymology / Q000473:pathology; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D058906:Purinergic P1 Receptor Agonists; C048599:N(6)-cyclopentyladenosine; D007770:L-Lactate Dehydrogenase; D000241:Adenosine