STIMULATION BY MN2-HORMONE EXOCYTOSIS AT AN INTRACELLULAR SITE( AND INHIBITION BY CD2+, ZN2+, NI2+, AND CO2+ IONS OF LUTEINIZING)

Direct intracellular effects of the divalent cations Mn2+, Cd2+, Co2+, Ni2+, and Zn2+ on pituitary hormone exocytosis in a permeabilized cel l system have not previously been investigated. We examined the effect s of these ions on LH exocytosis in primary sheep pituitary cells perm eabilized with Staphylococcal alpha-toxin. Mn2+ ions strongly stimulat ed LH release from permeabilized, but not intact, cells. Mn2+-stimulat ed LH release was ATP-dependent and sensitive to N-ethyl maleimide, in dicating that it represents true exocytosis. Hormone release triggered by Ca2+ was inhibited by Cd2+, Zn2+, Co2+, and Ni2+ ions. Half-maxima l inhibition of Ca2+-stimulated LH release was observed with 10 muM Cd 2+, 30 muM Zn2+, 0.3 mM Co2+, and 1 mM Ni2+. With the same order of po tency these ions inhibited LH release stimulated by Ba2+, Mn2+, or pho rbol ester plus cAMP, suggesting that they inhibit exocytosis at an in tracellular site common to all these stimuli.