Agonists selective for phosphoinositide-coupled receptors sensitize neurons to depolarization by L-2-amino-4-phosphonobutanoic acid (L-AP4).

Article date: 1991/8/2

PubMed ID: 1681998

Journal name: Brain research (ISSN: 0006-8993)


Exposure of hippocampal and cortical slices to quisqualate induces a 30- to 100-fold decrease in the half-maximal concentration of L-2-amino-4-phosphonobutanoic acid (L-AP4) required to depolarize neurons. This sensitization persists for hours and has previously been shown to be induced only by quisqualate, via the interaction of quisqualate with a 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-insensitive site. Here we tested the hypothesis that quisqualate may act on phosphoinositide (PI) metabolism to enhance the response to L-AP4, and found that sensitization to L-AP4 was induced by trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD), an agonist selective for PI-coupled excitatory amino acid receptors, and by carbachol and norepinephrine, agonists at other PI-coupled receptors. However, these compounds produced only a 2- to 5-fold sensitization to L-AP4, that was of shorter duration than that induced by quisqualate. These results suggest that sensitization to L-AP4 may be induced, at least in part, via PI-coupled receptors, and that the sensitivity of neurons to an excitatory amino acid agonist may be modified by heteroreceptor activation of the PI second messenger system.

Author List: Whittemore E R, Cotman C W

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Aminobutyrates; Neuromuscular Depolarizing Agents; Quinoxalines; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; phosphatidylinositol receptors; Cycloleucine; 1-amino-1,3-dicarboxycyclopentane; Ibotenic Acid; 6-Cyano-7-nitroquinoxaline-2,3-dione; Quisqualic Acid; Carbachol; 2-amino-4-phosphonobutyric acid; Norepinephrine;

Mesh terms: 6-Cyano-7-nitroquinoxaline-2,3-dione; Aminobutyrates/pharmacology; Animals; Carbachol/pharmacology; Cerebral Cortex/drug effects; Cycloleucine/analogs & derivatives; Hippocampus/drug effects; Ibotenic Acid/pharmacology; In Vitro Techniques; Male; Neuromuscular Depolarizing Agents/pharmacology; Neurons/drug effects; Norepinephrine/pharmacology; Quinoxalines/pharmacology; Quisqualic Acid/pharmacology; Rats; Rats, Inbred Strains; Receptors, Cell Surface/drug effects; Receptors, Cytoplasmic and Nuclear;

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