PMID- 8532176
OWN - NLM
STAT- MEDLINE
DCOM- 19960129
LR  - 20190726
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 34
IP  - 8
DP  - 1995 Aug
TI  - Presynaptic metabotropic glutamate receptors modulate 
      omega-conotoxin-GVIA-insensitive calcium channels in the rat medulla.
PG  - 953-64
AB  - We have previously demonstrated that the metabotropic glutamate receptor (mGluR) 
      agonist (1S,3R)-1 aminocyclopentane-1,3-dicarboxylate (ACPD) presynaptically 
      inhibits evoked glutamatergic EPSCs and GABAergic IPSCs in patch clamped rat 
      nucleus tractus solitarius (NTS) neurons recorded in this slices. The present 
      study investigated the pharmacology of the presynaptic mGluRs, the the voltage 
      dependent Ca2+ channel (VDCC) subtypes supporting neurotransmitter release, and 
      possible interactions between the two. Monosynaptic EPSCs or IPSCs were evoked by 
      electrical stimulation in the region of the tractus solitarius (TS). The effects 
      of the mGluR agonists ACPD, (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine 
      (L-CCG-I) and L-2-amino-4-phosphonobutyrate (AP4) were examined upon EPSCs. The 
      effects of the above compounds and quisqualate (QUIS) were examined upon IPSCs. 
      L-CCG-I proved the most potent inhibitor of EPSCs and IPSCs. The VDCC blockers 
      omega-AGA-IVA (AGA), omega-conotoxin GVIA (GVIA), omega-conotoxin MVIIC (MVIIC) 
      and nimodipine (NIM) were assessed for their ability to inhibit monosynaptic 
      EPSCs and IPSCs. EPSCs were inhibited by GVIA >> AGA > or = MVIIC. IPSCs were 
      inhibited by AGA > or = MVIIC >> GVIA. NIM was without effect on the EPSC or 
      IPSC. The potency of mGluR inhibition of evoked synaptic transmission was 
      assessed in the absence and following treatment with VDCC blockers. mGluR 
      agonists blocked a greater percentage of the EPSC or IPSC following treatment 
      with GVIA, but not the other VDCC antagonists, than under control conditions. We 
      have previously demonstrated that the postsynaptic inhibitory effects of mGluR 
      activation upon GABAA mediated currents can be mimicked by cyclic guanosine 
      monophosphate (cGMP) analogs. The cGMP-dependent protein kinase (PKG) inhibitors 
      H8 and Rp-8-4-chlorophenylthio-guanosine-3',5'-cyclic monophosphorothioate 
      (Rp-cG) blocked mGluR inhibition of GABAA mediated currents without blocking the 
      ability of mGluR agonists to inhibit the IPSC. The effect of L-CCGI was enhanced 
      following treatment with GVIA in the presence of Rp-cG, confirming a presynaptic 
      locus of mGluR mediated inhibition of the IPSC. In contrast, cGMP analogues 
      potentiate postsynaptic responses to glutamate agonists but depress the EPSC. As 
      with the mGluR agonists, the inhibition of the EPSC by cGMP was potentiated 
      following treatment with GVIA. These results suggest that presynaptic mGluR 
      reduce both glutamate release from afferent fibers and GABA release from 
      inhibitory interneurons following electrical stimulation in the region of the TS. 
      Although different VDCCs support the majority of glutamate and GABA release and 
      mGluR effects on release appear to utilize differing intracellular pathways, 
      presynaptic GVIA-insensitive VDCCs are favorably targeted for inhibition by mGluR 
      agonists.
FAU - Glaum, S R
AU  - Glaum SR
AD  - Department of Pharmacological and Physiological Sciences, University of Chicago, 
      IL 60637, USA.
FAU - Miller, R J
AU  - Miller RJ
LA  - eng
GR  - 2P50NS 21442-0981/NS/NINDS NIH HHS/United States
GR  - DA02121/DA/NIDA NIH HHS/United States
GR  - DA02575/DA/NIDA NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (Receptors, Presynaptic)
RN  - 92078-76-7 (omega-Conotoxin GVIA)
SB  - IM
MH  - Animals
MH  - Calcium Channel Blockers/*pharmacology
MH  - Calcium Channels/drug effects/*metabolism
MH  - Electrophysiology
MH  - In Vitro Techniques
MH  - Ion Channel Gating/drug effects
MH  - Medulla Oblongata/cytology/drug effects/*metabolism
MH  - Peptides/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Metabotropic Glutamate/agonists/antagonists & inhibitors/*metabolism
MH  - Receptors, Presynaptic/drug effects/*metabolism
MH  - Solitary Nucleus/cytology/drug effects/physiology
MH  - Synapses/drug effects/physiology
MH  - Synaptic Transmission/drug effects/physiology
MH  - omega-Conotoxin GVIA
EDAT- 1995/08/01 00:00
MHDA- 1995/08/01 00:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 1995/08/01 00:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
AID - 002839089500076I [pii]
AID - 10.1016/0028-3908(95)00076-i [doi]
PST - ppublish
SO  - Neuropharmacology. 1995 Aug;34(8):953-64. doi: 10.1016/0028-3908(95)00076-i.