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 Ca(2+)-activated cation and chloride conductances evoked by release of Ca2+ from intracellular stores of cultured neonatal dorsal root ganglion neurones. The aim of this study was to investigate metabotropic glutamate receptor (mGluR) mechanisms and evaluate a possible role for cyclic ADP-ribose as an intracellular signalling molecule. Glutamate and the metabotropic glutamate receptor agonist (1S, 3R)-ACPD-evoked transient depolarizations, Ca(2+)-activated inward currents and rises in intracellular Ca2+. The (1S, 3R)-ACPD-activated currents were insensitive to InsP3 signalling inhibitors, heparin and pentosan polysulphate. Intracellular application of ryanodine alone activated currents 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. Intracellular photo-release of cGMP and cyclic ADP-ribose mimicked the responses to mGluR receptor activation. Intracellular application of nicotinamide and W7 inhibited the responses to photo-released cGMP but did not prevent responses to mGluR activation. The cyclic ADP-ribose receptor antagonist 8-amino cyclic ADP-ribose attenuated responses to (1S, 3R)-ACPD, cGMP and cyclic ADP-ribose, but some Ca(2+)-activated inward currents were still observed in the presence of this antagonist. In conclusion, mGluR receptor activation, cGMP and cyclic ADP-ribose release Ca2+ from intracellular stores. Some evidence suggests that pharmacologically related pathways are involved.
Pollock
J
J
Department of Biomedical Sciences, University of Aberdeen, Foresterhill, Scotland, UK.
Crawford
J H
JH
Wootton
J F
JF
Seabrook
G R
GR
Scott
R H
RH
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose; D006152:Cyclic GMP / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010782:Photolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism* / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D018094:Receptors, Metabotropic Glutamate; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D003620:Dantrolene; D006152:Cyclic GMP; D002118:Calcium