ADENOSINE-A1-RECEPTOR ACTIVATION PREFERENTIALLY PROTECTS CULTURED CEREBELLAR NEURONS VERSUS ASTROCYTES AGAINST HYPOXIA-INDUCED DEATH

Administration of adenosine A1 receptor agonists in vivo is neuroprote ctive in various stroke models. Experiments using either mixed culture s of neurons and astrocytes or brain slices, in which several cell typ es are present, have demonstrated that activation of A1 receptors also is protective against hypoxia and/or hypoglycemia in vitro. Ln this s tudy, we have examined the effect of the A1 agonist cyclopentyladenosi ne (CPA) on cellular damage, measured by efflux of lactate dehydrogena se (LDH), in highly enriched primary cultures of either neurons or ast rocytes exposed to different metabolic insults. CPA reduced neuronal L DH release induced by a combination of hypoxia and substrate deprivati on (''simulated ischemia''; IC50 = 28 nM) or by hypoxia alone (IC50 = 170 nM). In contrast, CPA had no effect on neuronal damage induced by substrate deprivation alone, nor did it affect ischemic death to astro cytes. The neuroprotective effects of CPA during simulated ischemia an d hypoxia were reversed by the A1 antagonist 1, 3-dipropyl-8-cyclopent ylxanthine (DPCPX). These data demonstrate that activation of an adeno sine A1 receptor on neurons, but not astrocytes, is protective against cellular damage or death induced specifically by hypoxia as opposed t o other metabolic insults such as hypoglycemia.