Agonists selective for phosphoinositide-coupled receptors sensitize neurons to depolarization by L-2-amino-4-phosphonobutanoic acid (L-AP4).
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.
Department of Psychobiology, University of California, Irvine 92717.
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ER
Whittemore
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CW
Cotman
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007051:Ibotenic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear
D000613:Aminobutyrates; D009467:Neuromuscular Depolarizing Agents; D011810:Quinoxalines; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C040985:phosphatidylinositol receptors; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D007051:Ibotenic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016318:Quisqualic Acid; D002217:Carbachol; C012729:2-amino-4-phosphonobutyric acid; D009638:Norepinephrine