Endogenous adenosine reduces glutamatergic output from rods through activation of A2-like adenosine receptors

Salvatore L. Stella, Eric J. Bryson, Lucia Cadetti, Wallace B Thoreson

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Adenosine is released from retina in darkness; photoreceptors possess A2 adenosine receptors, and A2 agonists inhibit L-type Ca2+ currents (ICa) in rods. We therefore investigated whether A2 agonists inhibit rod inputs into second-order neurons and whether selective antagonists to A1, A2A, or A3 receptors prevent Ca2+ influx through rod ICa. [Ca2+]i changes in rods were assessed with fura-2. ICa in rods and light responses of rods and second-order neurons were recorded using perforated patch-clamp techniques in the aquatic tiger salamander retinal slice preparation. Consistent with earlier results using the A2 agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA), the A2A agonist CGS-21680 significantly inhibited ICa and depolarization-evoked [Ca2+]i increases in rods. The A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and A2A antagonist, ZM-241385, but not the A3 antagonist, VUF-5574, inhibited effects of adenosine on Ca2+ influx in rods. DPCPX and ZM-241385 also inhibited effects of CGS-21680, suggesting they both act at A2A receptors. Both A2 agonists, CGS-21680 and DPMA, reduced light-evoked currents in second-order neurons but not light-evoked voltage responses of rods, suggesting that activation of A2 receptors inhibits transmitter release from rods. The inhibitory effects of CGS-21680 on both depolarization-evoked Ca2+ influx and light-evoked currents in second-order neurons were antagonized by ZM-241385. By itself, ZM-241385 enhanced the light-evoked currents in second-order neurons, suggesting that endogenous levels of adenosine inhibit transmitter release from rods. The effects of these drugs suggest that endogenous adenosine activates an A2-like adenosine receptor on rods leading to inhibition of ICa, which in turn inhibits L-glutamate release from rod photoreceptors.

Original languageEnglish (US)
Pages (from-to)165-174
Number of pages10
JournalJournal of Neurophysiology
Volume90
Issue number1
DOIs
StatePublished - Jul 1 2003

Fingerprint

Adenosine A2 Receptors
varespladib methyl
Adenosine
Neurons
Light
Adenosine A2 Receptor Agonists
Ambystoma
Retinal Rod Photoreceptor Cells
Fura-2
Darkness
Patch-Clamp Techniques
Retina
Glutamic Acid
2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
ZM 241385
Pharmaceutical Preparations
1,3-dipropyl-8-cyclopentylxanthine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Endogenous adenosine reduces glutamatergic output from rods through activation of A2-like adenosine receptors. / Stella, Salvatore L.; Bryson, Eric J.; Cadetti, Lucia; Thoreson, Wallace B.

In: Journal of Neurophysiology, Vol. 90, No. 1, 01.07.2003, p. 165-174.

Research output: Contribution to journalArticle

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