11784755

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1

Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca(2+) currents (I(Ca)) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca(2+) 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 I(Ca) and intracellular Ca(2+) increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both I(Ca) and the [Ca(2+)]i increase evoked by depolarization in a dose-dependent manner with approximately 25% inhibition at 50 microM. An A2-selective agonist, (N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, (R)-N(6)-(1-methyl-2-phenylethyl)adenosine and N(6)-2-(4-aminophenyl)ethyladenosine, also inhibited I(Ca) and depolarization-induced [Ca(2+)]i increases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both I(Ca) and the depolarization-evoked [Ca(2+)]i increase in rods. The results suggest that activation of A2 receptors stimulates PKA to inhibit L-type Ca(2+) channels in rods resulting in a decreased Ca(2+) influx that should suppress glutamate release.

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MEDLINE

0022-3077

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NLM

351-60

pubmed-meshheading:11784755-Adenosine, pubmed-meshheading:11784755-Adenosine Triphosphate, pubmed-meshheading:11784755-Animals, pubmed-meshheading:11784755-Calcium, pubmed-meshheading:11784755-Calcium Channels, L-Type, pubmed-meshheading:11784755-Cell Separation, pubmed-meshheading:11784755-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:11784755-Dose-Response Relationship, Drug, pubmed-meshheading:11784755-Enzyme Inhibitors, pubmed-meshheading:11784755-Fluorescent Dyes, pubmed-meshheading:11784755-Ion Transport, pubmed-meshheading:11784755-Patch-Clamp Techniques, pubmed-meshheading:11784755-Potassium, pubmed-meshheading:11784755-Purinergic P1 Receptor Agonists, pubmed-meshheading:11784755-Receptors, Purinergic P1, pubmed-meshheading:11784755-Retina, pubmed-meshheading:11784755-Retinal Rod Photoreceptor Cells, pubmed-meshheading:11784755-Signal Transduction, pubmed-meshheading:11784755-Urodela

A2 adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina.

Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't