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PMID: 7741717 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Metabotropic glutamate receptor analogues inhibit p[NH]ppG-stimulated phospholipase C activity in bovine brain coated vesicles: involvement of a pertussis toxin-sensitive G-protein.

The Biochemical journal ·Vol. 307 ( Pt 3) ·1995-05-01 ·Pages 851-7

Martín M, Sanz JM, Ros M, Cubero A

Abstract

Guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG)-stimulated phospholipase C (PLC) activity in bovine brain coated vesicles is inhibited by glutamate agonists. In the present study we show that quisqualic acid (QA), (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylate (trans-ACPD), glutamic acid and ibotenic acid inhibited p[NH]ppG-stimulated PLC by 44, 41, 36 and 25% respectively. Carbachol also produced an inhibition of p[NH]ppG-stimulated PLC by 45%. The inhibition caused by trans-ACPD and QA was dose-dependent. DL-2-Amino-3-phosphonopropionic acid and (RS)-alpha-methyl-4-carboxyphenylglycine, specific antagonists of metabotropic glutamate receptors (mGluRs), abolished these inhibitory effects. trans-ACPD inhibition of p[NH]ppG-stimulated PLC was also observed in the presence of ionotropic glutamate receptor antagonists. When carbachol and QA or trans-ACPD were combined, additive inhibitory effects were observed. Preincubation of bovine brain coated vesicles with pertussis toxin abolished the inhibitory effects of mGluR analogues and carbachol on p[NH]ppG-stimulated PLC activity. The presence of Gs alpha and pertussis toxin substrates, Gi alpha and Go alpha subunits as well as PLC beta 1 in bovine brain coated vesicles has been confirmed by immunoblot. These results support the coupling of mGluRs to a PLC in an inhibitory manner through a pertussis toxin-sensitive G-protein in bovine brain coated vesicles.

MeSH Terms
Animals Brain/drug effects,enzymology Cattle Guanylyl Imidodiphosphate/pharmacology Isoenzymes/antagonists & inhibitors,metabolism Liposomes Membranes/enzymology Pertussis Toxin Receptors, Glutamate/metabolism Stimulation, Chemical Type C Phospholipases/antagonists & inhibitors,metabolism Virulence Factors, Bordetella/pharmacology
Chemicals
Isoenzymes Liposomes Receptors, Glutamate Virulence Factors, Bordetella Guanylyl Imidodiphosphate Pertussis Toxin Type C Phospholipases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Martín M
Departamento de Inorgánica Orgánica y Bioquímica, Facultad de Químicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
Sanz J M
Ros M
Cubero A
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3070851
Published
1995-05-01
Pages
851-7
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1136726
Subset
IM
External Links
PubMed source DOI: 10.1042/bj3070851 PMC Full Text View journal details
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