Excitatory amino acids inhibit stimulated phosphoinositide hydrolysis in the rat prefrontal cortex.
In rat prefrontal cortical slices, the excitatory amino acids N-methyl-D-aspartate (NMDA), ibotenate, L-aspartate, quisqualate, kainate and L-glutamate inhibit carbachol-induced phosphoinositide hydrolysis as measured by the accumulation of [3H]inositol-1-phosphate ([3H]IP1). NMDA dose-dependently inhibited the carbachol response (IC50 = 14.4 microM), and this inhibition was blocked by the NMDA receptor antagonist D,L-aminophosphonovaleric acid. Lowering medium Na+ concentration to 10 mM or exposing slices to pertussis toxin alleviated the inhibitory effect of NMDA on carbachol-induced [3H]IP1 formation. Serotonin-induced stimulation of [3H]IP1 was also inhibited by NMDA; in contrast, stimulation by norepinephrine, epinephrine or dopamine was unaffected. The results suggest that excitatory amino acids, besides their traditional role as stimulatory substances, can also act to inhibit the production of 2nd messengers activated by certain neurotransmitters in the brain.
Noble
E P
EP
Alcohol Research Center, University of California, Los Angeles 90024.
Sincini
E
E
Bergmann
D
D
ten Bruggencate
G
G
D000600:Amino Acids, Dicarboxylic / Q000502:physiology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate; D018377:Neurotransmitter Agents / Q000502:physiology; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage; D010277:Parasympathomimetics / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D012964:Sodium / Q000502:physiology; D013403:Sugar Phosphates / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000600:Amino Acids, Dicarboxylic; D007295:Inositol Phosphates; D018377:Neurotransmitter Agents; D014179:Neurotransmitter Uptake Inhibitors; D010277:Parasympathomimetics; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D013403:Sugar Phosphates; D010566:Virulence Factors, Bordetella; C002647:inositol 1-phosphate; D001224:Aspartic Acid; D016202:N-Methylaspartate; D002772:Cholera Toxin; D012964:Sodium; D037342:Pertussis Toxin