Localization and possible function of P2Y4 receptors in the rodent retina

doi:10.1016/j.neuroscience.2008.06.035

Neuroscience

Volume 155, Issue 4, 9 September 2008, Pages 1262-1274

https://doi.org/10.1016/j.neuroscience.2008.06.035 Get rights and content

Abstract

Extracellular ATP acts as a neurotransmitter in the retina, via the activation of ionotropic P2X receptors and metabotropic P2Y receptors. The expression of various P2X and P2Y receptor subtypes has been demonstrated in the retina, but the localization of P2Y receptors and their role in retinal signaling remains ill defined. In this study, we were interested in determining the localization of the P2Y₄ receptor subtype in the rat retina, and using the electroretinogram (ERG) to assess whether activation of these receptors modulated visual transmission. Using light and electron microscopy, we demonstrated that P2Y₄ receptors were expressed pre-synaptically in rod bipolar cells and in processes postsynaptic to cone bipolar cells. Furthermore, we show that the expression of P2Y₄ receptors on rod bipolar cell axon terminals is reduced following dark adaptation, suggesting receptor expression may be dependent on retinal activity. Finally, using the electroretinogram, we show that intravitreal injection of uridine triphosphate, a P2Y receptor agonist, decreases the amplitude of the rod PII, supporting a role for P2Y receptors in altering inner retinal function. Taken together, these results suggest a role for P2Y₄ receptors in the modulation of inner retinal signaling.

Section snippets

Animal and tissue preparation

All animal experimentation was performed in accordance with the institutional animal experimentation ethics committee and with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Efforts were made to minimize the number and suffering of animals used.

Retinae from adult Sprague–Dawley rats were used to evaluate the light and ultrastructural localization of P2Y₄Rs in the retina. Rats were obtained from the animal house facility of the Department of Anatomy and Cell

The P2Y₄R is expressed in mammalian retinae

Fig. 1 shows a micrograph of lightly fixed adult rat retina that has been immunocytochemically labeled for the P2Y₄R. P2Y₄ immunoreactivity was observed in both the outer and IPLs. In particular, putative rod bipolar cell axon terminals were intensely labeled in the IPL. We also found extrasynaptic labeling of putative rod bipolar cell somata in the INL, adjacent to the outer plexiform layer (OPL). There was also diffuse extrasynaptic labeling of some cells in the INL, adjacent to the IPL that

Discussion

The major findings of this study are that P2Y₄Rs are heavily expressed within the inner retina, particularly within the dendrites and axon terminals of rod bipolar cells and in cells post-synaptic to cone bipolar cells. Moreover, altering neural activity with light levels alters P2Y₄R expression within rod bipolar cell axon terminals, and injection of the agonist, UTP, caused a substantial reduction in the amplitude of the rod and cone PII. These findings implicate P2Y₄Rs in the modulation of

Acknowledgments

This work was supported by a grant from the National Health and Medical Research Council (NHMRC; #350434 to E.L.F.).

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Sensory systemLocalization and possible function of P2Y4 receptors in the rodent retina

Abstract

Section snippets

Animal and tissue preparation

The P2Y4R is expressed in mammalian retinae

Discussion

Acknowledgments

Vision Res

J Biol Chem

Biochim Biophys Acta

Vision Res

Neuron

Brain Res Mol Brain Res

Vision Res

Neuron

Vision Res

Eur J Pharmacol

Prog Retin Eye Res

Trends Neurosci

Pharmacol Ther

Vision Res

International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy

Pharmacol Rev

Adaptation-dependent plasticity of rod bipolar cell axon terminal morphology in the rat retina

Cell Tissue Res

Molecular cloning and characterization of rat P2Y4 nucleotide receptor

Br J Pharmacol

Differential expression of the presynaptic cytomatrix protein bassoon among ribbon synapses in the mammalian retina

Eur J Neurosci

Ganglion cell contributions to the rat full-field electroretinogram

J Physiol

Monocarboxylate transport inhibition alters retinal function and cellular amino acid levels

Eur J Neurosci

Electron microscopic analysis of the rod pathway of the rat retina

J Comp Neurol

The P2Y4 receptor forms homo-oligomeric complexes in several CNS and PNS neuronal cells

Purinergic Signalling

Demonstration of P2Y4 purinergic receptors in the HT-29 human colon cancer cell line

Auton Aautacoid Pharmacol

Temporal modulation of scotopic visual signals by A17 amacrine cells in mammalian retina in vivo

J Neurophysiol

Organization of the primate retina: electron microscopy

Proc R Soc Lond B Biol Sci

Quantitative analysis of intravitreal injections in the rat

Curr Eye Res

Synaptic localization of NMDA receptor subunits in the rat retina

J Comp Neurol

GABAA and GABAC receptors on mammalian rod bipolar cells

J Comp Neurol

Indoleamine-accumulating amacrine cells are presynaptic to rod bipolar cells through GABA(C) receptors PG-155-67

J Comp Neurol

Identification of P2Y receptor subtypes in human muller glial cells by physiology, single cell RT-PCR, and immunohistochemistry

Invest Ophthalmol Vis Sci

Expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes in the rat retina

Invest Ophthalmol Vis Sci

Localization of GABAA receptors in the rabbit retina

Cell Tissue Res

Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity

J Comp Neurol

Sensory system
Localization and possible function of P2Y₄ receptors in the rodent retina

The P2Y₄R is expressed in mammalian retinae