title: Excitatory amino acids (EAAs) stimulate phosphatidylinositol turnover in adult rat striatal slices: interaction between NMDA and EAA metabotropic receptors.
abstract: The effect of excitatory amino acids (EAAs) on phosphatidylinositol (PI) turnover in adult rat striatal slices was investigated. Quisqualic acid (QA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainic acid (KA), ibotenic acid (IBO) and N-methyl-D-aspartic acid (NMDA) maximally increased inositol phosphate (IP) formation at 10 microM while trans-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) was maximally effective at 100 microM. The NMDA channel blocker dizolcipine (MK-801) counteracted the effect of NMDA 10 microM and IBO 10 microM while it potentiated that of IBO 100 microM and IBO 1000 microM. Conversely, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prevented the effect of AMPA and KA and reduced that of QA (all at 10 microM). Lowering extracellular Ca2+ concentrations ([Ca2+]0) differentially affected the PI response to EAAs. The ACPD 30 microM effect was unchanged at low [Ca2+]0 (but abolished when EGTA 2 mM was added), while that of ACPD 100 microM was halved in 0.1 mM and almost abolished in a nominally free Ca2+ medium. NMDA 10 microM and AMPA 10 microM were ineffective at low [Ca2+]0 while NMDA 100 microM, ineffective in a 1.2 mM Ca2+ medium, strongly stimulated IP formation in 0.1 mM Ca2+ but not in a nominally free Ca2+ medium. The effect of NMDA on EAA metabotropic receptor agonist stimulated PI turnover was also studied. NMDA 10 microM potentiated the effect of ACPD 30 microM. This positive cooperation persisted at low [Ca2+]0 but not in the presence of EGTA. Conversely, NMDA 100 microM prevented the effect of ACPD 100 microM. This negative interference was reversed when Ca2+ was omitted from the medium. This study shows that in the adult rat striatum both EAA metabotropic and ionotropic receptor activation increases IP formation. A positive and negative interaction between NMDA and metabotropic receptor activation was also found to regulate PI turnover. The role of [Ca2+]0 in subserving the PI response to EAAs was made evident.
authors.affiliation: Institute of Pharmacology, University of Ferrara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Morari
authors.forename: M
authors.initials: M
authors.lastname: Menegale
authors.forename: G
authors.initials: G
authors.lastname: Caló
authors.forename: L
authors.initials: L
authors.lastname: Ferraro
authors.forename: C
authors.initials: C
authors.lastname: Tomasini
authors.forename: C
authors.initials: C
authors.lastname: Bianchi
authors.forename: L
authors.initials: L
authors.lastname: Beani
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000596:Amino Acids; D010716:Phosphatidylinositols; D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate; D002118:Calcium