title: Phospholipase A and Somatostatin Release are Activated in Response to N-Methyl-D-Aspartate Receptor Stimulation in Hypothalamic Neurons in Primary Culture.
abstract: Abstract We have recently shown that glutamate primarily induces somatostatin release in hypothalamic neurons through N-methyl-D-aspartate (NMDA)-type receptor sites. Here we report that glutamate and NMDA also stimulate the release of [(3)H]arachidonic acid in a dose-dependent manner. The NMDA-induced effects (arachidonic acid release and somatostatin secretion) were both inhibited by MK-801, an NMDA receptor-type antagonist, or mepacrine, a phospholipase A(2) inhibitor. In addition, mepacrine was able to inhibit A23187-stimulated arachidonic acid release and somatostatin secretion. p-Bromophenacylbromide, another phospholipase A(2) inhibitor, also blocked NMDA-induced secretion of somatostatin. However, responses to NMDA were unaffected by H7 (inhibitor of protein kinase C), nordihydroguaiaretic acid or indomethacin (inhibitors of lipoxygenase and cyclooxygenase). Melittin, a phospholipase A(2) activator, was found to stimulate both responses, but omission of extracellular Ca(2+) from the incubation media strongly reduced melittin-induced somatostatin release. Six-h pertussis toxin pretreatment did not significantly reduce the action of NMDA on either of the two parameters studied. High-performance liquid chromatography analysis of [(3)H]metabolites released in the medium after NMDA stimulation revealed that [(3)H]arachidonic acid was the only detectable metabolite. External addition of arachidonic acid increased the release of somatostatin, whereas E(2) and F(2)alpha prostaglandins had no effect. Our results show a close correlation between arachidonic acid release and somatostatin secretion, the two parameters we investigated.
authors.affiliation: Unité de Neurobiologie Endocrinologique, CNRS UA 1197, Université de Montpellier II, 34095 Montpellier Cédex 5, France.
authors.forename: F
authors.initials: F
authors.lastname: Rage
authors.forename: J P
authors.initials: JP
authors.lastname: Pin
authors.forename: L
authors.initials: L
authors.lastname: Tapia-Arancibia