Adenosine modulation of [Ca 2+] i in cerebellar granular cells: multiple adenosine receptors involved

Abstract

Elimination of adenosine by addition of adenosine deaminase (ADA) to the media leads to alterations in intracellular free calcium concentration ([Ca 2+] i) in cerebellar granular cells. Adenosine deaminase brings about increases or decreases in [Ca 2+] i depending on the previous activation state of the cell. These effects are dependent on the catalytic activity of adenosine deaminase, since its previous catalytic inactivation with Hg 2+ prevents the above-mentioned changes in intracellular calcium. Extracellular calcium is required for the increase in [Ca 2+] i promoted by ADA. This rise is insensitive to thapsigargin, but sensitive to micromolar concentrations of Ni 2+. Toxins specific for L, N and P/Q calcium channels do not overtly reduce this effect. N 6-Cyclopentyl adenosine (CPA), an A 1 receptor agonist, produces a partial reversion of ADA effects, while CGS21680, A 2A/A 2B receptor agonist, slightly enhances them. Expression of A 1, A 2A, A 2B and A 3 adenosine receptor mRNAs was detected in cerebellar granular cell cultures. These results suggest that adenosine modulate [Ca 2+] i in cerebellar granule cells through different adenosine receptor subtypes which, at least in part, seem to act through R-type calcium channels.