Stimulation by Mn2+ and inhibition by Cd2+, Zn2+, Ni2+, and Co2+ ions of luteinizing hormone exocytosis at an intracellular site

Abstract

Direct intracellular effects of the divalent cations Mn2+, Cd2+, Co2+, Ni2+, and Zn2+ on pituitary hormone exocytosis in a permeabilized cell system have not previously been investigated. We examined the effects of these ions on LH exocytosis in primary sheep pituitary cells permeabilized with Staphylococcal alpha-toxin. Mn2+ ions strongly stimulated LH release from permeabilized, but not intact, cells. Mn(2+)-stimulated LH release was ATP-dependent and sensitive to N-ethyl maleimide, indicating that it represents true exocytosis. Hormone release triggered by Ca2+ was inhibited by Cd2+, Zn2+, Co2+, and Ni2+ ions. Half-maximal inhibition of Ca(2+)-stimulated LH release was observed with 10 microM Cd2+, 30 microM Zn2+, 0.3 mM Co2+, and 1 mM Ni2+. With the same order of potency these ions inhibited LH release stimulated by Ba2+, Mn2+, or phorbol ester plus cAMP, suggesting that they inhibit exocytosis at an intracellular site common to all these stimuli.