Actions of Excitatory Amino Acids on Somatostatin Release from Cortical Neurons in Primary Cultures

Abstract

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.

Phospholipase A2 and Somatostatin Release are Activated in Response to N‐Methyl‐D‐Aspartate Receptor Stimulation in Hypothalamic Neurons in Primary Culture

“…p-Bromophenacylbromide (pBPB) (100 pM), an inhibitor of the phospholipase A, active site, also inhibited NMDAinduced SRIF release (Table3). As we observed in previous studies (3,45), spontaneous SRIF release decreased in the presence of TTX ( I pM), without any significant modification in arachidonic acid release.…”

“…Although it is difficult to speculate on the mechanisms by which the exocytotic proccss occurs, NMDA-induced depolarization could possibly initiate the exocytotic response. Indeed, we have already demonstrated that glutamate is unable to stimulate SRIF release in Ca2+-free medium (45). Ca2+ entry through the NMDA receptor complex channel (4) could activate phospholip a x A,, with a concomitant release of arachidonic acid and SRIF exocytosc, however both effects are not necessarily correlated.…”

β‐Amyloid increases somatostatin expression in cultured cortical neurons

“…Accordingly, the data presented here exclude any possible interference of glial cell. SST expressions and its release in response to other neurotoxins, such as NMDA, have been characterized in depth (Tapia‐Arancibia and Astier 1989; Ham et al. 1991, 1993; Patel et al.…”

Somatostatin and Somatostatin-Containing Neurons in Shaping Neuronal Activity and Plasticity

“…Early observations by Gamse et al ( 1980 ), revealed that somatostatin is released from cultured hypothalamic cells even in the absence of exogenous stimuli, in calcium- dependent manner. Tapia-Arancibia and Astier ( 1989 ) showed that increase of SOM release is achieved by membrane depolarization. Fontana et al ( 1996 ) have shown that in hippocampus, glutamate can stimulate somatostatin release through the activation of ionotropic NMDA and AMPA receptors; furthermore, experiments by Rage et al ( 1994 ) revealed that in primary cultures of hypothalamic neurons release of somatostatin was elicited by NMDA application.…”