Metabotropic glutamate receptor activation and intracellular cyclic ADP-ribose release Ca2+ from the same store in cultured DRG neurones

The whole cell patch clamp technique has been used to record Ca2+-activated cation and chloride conductances evoked by release of Ca2+ from intracellu lar stores of cultured neonatal dorsal root ganglion neurones. The aim of t his study was to investigate metabotropic glutamate receptor (mGluR) mechan isms and evaluate a possible role for cyclic ADP-ribose as an intracellular signalling molecule. Glutamate and the metabotropic glutamate receptor ago nist (1S,3R)-ACPD-evoked transient depolarizations, Ca2+-activated inward c urrents and rises in intracellular Ca2+. The (1S,3R)-ACPD-activated current s were insensitive to InsP(3) signalling inhibitors, heparin and pentosan p olysulphate. Intracellular application of ryanodine alone activated current s in this study and proved a difficult tool to use as a potential inhibitor of cyclic ADP-ribose-mediated responses. However, intracellular dantrolene did attenuate both (1S,3R)-ACPD and cyclic ADP-ribose responses. Intracell ular photorelease of cGMP and cyclic ADP-ribose mimicked the responses to m GluR receptor activation. Intracellular application of nicotinamide and W7 inhibited the responses to photoreleased cGMP but did not prevent responses to mGluR activation. The cyclic ADP-ribose receptor antagonist 8-amino cyc lic ADP-ribose attenuated responses to (1S,3R)-ACPD, cGMP and cyclic ADP-ri bose, but some Ca2+-activated inward currents were still observed in the pr esence of this antagonist. In conclusion, mGluR receptor activation, cGMP a nd cyclic ADP-ribose release Ca2+ from intracellular stores. Some evidence suggests that pharmacologically related pathways are involved. (C) Harcourt Publishers Ltd 1999.