Glutamate stimulates somatostatin release from diencephalic neurons in primary culture.
The action of excitatory amino acid agonists on endogenous somatostatin release was examined in primary cultures of rat diencephalic neurons. Increasing concentrations of glutamate stimulated somatostatin release in a dose-dependent manner. Since this effect was decreased by Mg2+, all experiments were performed in Mg2+-free media. We found that excitatory amino acid agonists evoked somatostatin release in the following order of potency: quisqualate greater than glutamate = N-methyl-D-aspartate (NMDA) greater than kainate, as calculated from the dose-response curves. The increase in somatostatin release elicited by glutamate or NMDA was selectively antagonized by DL-2-amino-5-phosphonovaleric acid and by thyenyl-phencyclidine, two specific antagonists of NMDA receptors. The NMDA effect was strongly inhibited: in a competitive manner by APV and in a noncompetitive manner by TCP with IC50 of 90 microM and 0.2 microM, respectively. Glutamate-induced somatostatin release was not blocked by tetrodotoxin (1 microM) suggesting that tetrodotoxin-sensitive sodium-dependent action potentials are not involved in this effect. Our data suggest the presence of functionally active excitatory amino acid receptors in somatostatinergic neurons. Glutamate seems to exert its stimulatory action on somatostatin release essentially through NMDA type receptor sites.
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D004027:Diencephalon / Q000166:cytology* / Q000196:embryology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D013004:Somatostatin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D005971:Glutamates; D010069:Oxadiazoles; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D013004:Somatostatin; D016202:N-Methylaspartate; D014701:Veratridine; D015763:2-Amino-5-phosphonovalerate; C012058:tenocyclidine; D016318:Quisqualic Acid; D014633:Valine; D008274:Magnesium; D010622:Phencyclidine; D011188:Potassium; D007608:Kainic Acid