Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca2+ currents (ICa) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca2+ channels that regulate the release of L-glutamate. In the retina, adenosine is released in the dark when L-glutamate release is maximal. We tested whether adenosine inhibits ICa and intracellular Ca2+ increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both ICa and the [Ca2+]i increase evoked by depolarization in a dose-dependent manner with ∼25% inhibition at 50 μM. An A2-selective agonist, (N6- [2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, (R)-N6-(1-methyl-2-phenylethyl)adenosine and N6-2-(4-aminophenyl)ethyladenosine, also inhibited ICa and depolarization-induced [Ca2+]i increases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both ICa and the depolarization-evoked [Ca2+]i increase in rods. The results suggest that activation of A2 receptors stimulates PKA to inhibit L-type Ca2+ channels in rods resulting in a decreased Ca2+ influx that should suppress glutamate release.
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