Interaction between mGluR8 and calcium channels in photoreceptors is sensitive to pertussis toxin and occurs via G protein betagamma subunit signaling.

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 Gi/o/z proteins and Gt protein/transducin, or a G protein betagamma subunit-inhibiting peptide abolished this activity. Preincubation of cells with cholera toxin (CTX), an activator of Gs 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 betagamma subunit. The absence of Go and Gz proteins, as reported previously, implies a novel potential interaction between Gi2 and/or Gt protein/transducin and mGluR8 in photoreceptors. These results have potential implications for the regulatory function and pharmacologic targeting of mGluR8 in photoreceptors.