Endogenous adenosine reduces glutamatergic output from rods through activation of A2-like adenosine receptors.
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.
Stella
Salvatore L
SL
Department of Pharmacology and Department of Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5540, USA. sstella@mednet.ucla.edu
Bryson
Eric J
EJ
Cadetti
Lucia
L
Thoreson
Wallace B
WB
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling; D004594:Electrophysiology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012160:Retina / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission; D014562:Caudata
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D018698:Glutamic Acid; D000241:Adenosine; D002118:Calcium