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Interaction between mGluR8 and Calcium Channels in Photoreceptors Is Sensitive to Pertussis Toxin and Occurs Via G Protein ß Subunit Signaling

¹From the Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; and the ²North Texas Eye Research Institute, Fort Worth, Texas.

PURPOSE. The most recently identified metabotropic glutamate receptor (mGluR), type 8 mGluR (mGluR8), has been identified functionally as a presynaptic autoreceptor in rod photoreceptors. This study analyzed the mechanism of action underlying mGluR8 activity and modulation of the cytosolic Ca²⁺ concentration in mouse photoreceptors.

METHODS. The cytosolic Ca²⁺ concentration of acutely isolated rod photoreceptors was monitored optically with microspectrofluorimetry and in the presence of modulators of G protein activity.

RESULTS. mGluR8 activation by the group III mGluR agonists L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate or the physiological ligand L-glutamate produced a decrease in influx of extracellular Ca²⁺ into the cytosol. Pretreatment of isolated rod photoreceptors with the G protein uncoupler suramin or pertussis toxin, which inactivates G_i/o/z proteins and G_t protein/transducin, or a G protein ß subunit–inhibiting peptide abolished this activity. Preincubation of cells with cholera toxin (CTX), an activator of G_s protein, had no effect.

CONCLUSIONS. These results suggest that the function of mGluR8 of modulating the cytosolic Ca²⁺ concentration and thereby potentially the release of neurotransmitter from rod spherules, the axon terminal systems of rod photoreceptors, is mediated by a pertussis toxin–sensitive G protein potentially via the ß subunit. The absence of G_o and G_z proteins, as reported previously, implies a novel potential interaction between G_i2 and/or G_t protein/transducin and mGluR8 in photoreceptors. These results have potential implications for the regulatory function and pharmacologic targeting of mGluR8 in photoreceptors.

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