Actions of excitatory amino acids on somatostatin release from cortical neurons in primary cultures.
L-Glutamate, N-methyl-D-aspartic acid (NMDA), quisqualate, and kainate were found to increase endogenous somatostatin release from primary cultures of rat cortical neurons in a dose-dependent manner. The rank order of potency calculated from the dose-response curves was quisqualate greater than glutamate = NMDA greater than kainate, with EC50 values of 0.4, 20, and 40 microM, respectively. Alanine, glutamine, and glycine did not modify the release of somatostatin. The stimulation of somatostatin release elicited by L-glutamate was Ca2+ dependent, was decreased by Mg2+, and was blocked by DL-amino-5-phosphonovaleric acid (APV) and thienylphencyclidine (TCP), two specific antagonists of NMDA receptors. The NMDA stimulatory effect was strongly inhibited by APV in a competitive manner (IC50 = 50 microM) and by TCP in a noncompetitive manner (IC50 = 90 nM). The release of somatostatin induced by the excitatory amino acid agonists was not blocked by tetrodotoxin (1 microM), a result suggesting that tetrodotoxin-sensitive, sodium-dependent action potentials are not involved in the effect. Somatostatin release in response to NMDA was potentiated by glycine, but the inhibitory strychnine-sensitive glycine receptor did not appear to be involved. Our data suggest that glutamate exerts its stimulatory action on somatostatin release essentially through an NMDA receptor subtype.
Tapia-Arancibia
L
L
Unité de Neurobiologie Endocrinologique, UA 1197, CNRS, Université de Montpellier II, France.
Astier
H
H
D000409:Alanine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005333:Fetus; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005973:Glutamine / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D013004:Somatostatin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D000596:Amino Acids; D005971:Glutamates; D018377:Neurotransmitter Agents; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D013004:Somatostatin; D016202:N-Methylaspartate; D014701:Veratridine; D008274:Magnesium; D000409:Alanine; D005998:Glycine