Evidence for swelling-induced adenosine and adenine nucleotide release in rat cerebral cortex exposed to monocarboxylate-containing or hypotonic artificial cerebrospinal fluids

Abstract

Recent reports have described a swelling-induced release of adenosine triphosphate (ATP) from a variety of non-nervous system cell types, which may be involved in the regulatory volume decrease (RVD) response. The present study examined the effects of swelling induced by applications of hypotonic or monocarboxylic acid containing artificial cerebrospinal fluid (aCSF) on the release of adenosine nucleotides and adenosine from the in vivo rat cerebral cortex using a cortical cup technique. Hypotonic aCSF (25 mM NaCl) elicited a significant increase in adenosine, but not adenine nucleotide, release. Applications of sodium l-lactate, pyruvate, or acetate (all 20 mM) evoked increases in adenine nucleotides but not adenosine. d-Lactate (20 mM) enhanced adenosine and ATP release. Inhibition of the plasma membrane monocarboxylate transporter with cyano-4-hydroxycinnamate (4-CIN, 2 mM) blocked the effects of l-lactate on purine release. These in vivo results demonstrate that osmoregulatory processes in cortical cells evoke an efflux of adenine nucleotides and/or adenosine. In that these purines activate a variety of receptors, it is possible that they may function as autocrine or paracrine signaling agents, facilitating volume regulation and enhancing local blood flow.