Release of prostaglandin E₂ from the hypothalamus depends on extracellular Ca²⁺ availability: Relation to LHRH release

The present experiments were performed to investigate the role of extracellular Ca²⁺ in the process of prostaglandin E₂ (PGE₂) release from the median eminence (ME) of the hypothalamus. Changes in the release of LHRH were also evaluated. Incubation of ME fragments with different concentrations of K⁺ induced a dose-related increase in PGE₂ and LHRH release. The effect of K⁺ depended upon the Ca²⁺ concentration in the incubation medium. A Ca²⁺ concentration of 0.1 mM was sufficient to permit a significant response in both PGE₂ and LHRH release to K⁺. The effect of a maximal K⁺ concentration (56 mM) was almost completely obliterated by omitting Ca²⁺ from the incubation medium and by chelating the remaining Ca²⁺ with EDTA or EGTA. The Ca²⁺ ionophore A23187, tested at different concentrations (1-50 μM) significantly increased the release of both PGE' and LHRH from the ME in a Ca^{2 +} -dependent manner. A Ca²" concentration of 0.25 mM allowed maximal LHRH response to the ionophore, but permitted only a partial (50%) PGE₂ response. Blockade of Ca²⁺ channels with Verapamil, a Ca²⁺ entry blocker, prevented the effect of K⁺ on both PGE₂ and LHRH release in a dose-dependent manner. The results demonstrate that release of PGE: From ME nerve terminals depends upon the concentration of extracellular Ca²⁺ and suggest that PGE₂ release is initiated by an increase in Ca²⁺ influx to the terminals. In addition, the data provide further evidence that release of LHRH is, to a significant extent, a function of Ca²⁺ influx through Ca²⁺ voltage-dependent channels.