The effects of ionotropic agonists of excitatory amino acids on the release of arginine vasopressin in rat hypothalamic slices

The effects of ionotropic excitatory amino acids agonists on the release of vasopressin from rat hypothalamic slices were studied. Incubation with increasing doses of NMDA, kainate or AMPA decreased the release of vasopressin in a dose-dependent manner. The values of the IC50 were 1.0, 9.6, or 3.7 x 10(-8) M, respectively. The inhibitory effect of the various excitatory amino acids tested was blocked by coincubation with their respective antagonists. Vasopressin secretion was stimulated to 140.3 +/- 7.6% of controls when the slices were obtained from chronically (7 days) salt-loaded rats. Addition of 1 x 10(-7) M NMDA or 1 x 10(-6) M kainate to the incubation medium antagonized the salt loading-induced increase in vasopressin release. Incubation with 1 x 10(-4) M tetrodotoxin did not change basal vasopressin release, but it blocked the decrease in vasopressin secretion induced by 1 x 10(-7) M NMDA or 1 x 10(-6) M kainate or 1 x 10(-6) M AMPA. Incubation with 1 x 10(-5) M phaclophen (a GABA(B) antagonist) and 1 x 10(-5) M bicuculline (a GABA(A) antagonist) was without effect on basal vasopressin secretion while it reversed the inhibition of vasopressin release induced by 1 x 10(-7) M NMDA. Incubation with 1 x 10(-6) M GABA alone decreased vasopressin secretion to 64.6 +/- 6.9% of control values. The inhibitory effect of GABA did not change when 1 x 10(-7) M NMDA was added to the incubation medium. These findings demonstrate that ionotropic excitatory amino acids agonists inhibit vasopressin secretion from hypothalamic slices. They strongly suggest that this inhibitory effect is mediated through local GABAergic interneurones.