6R-Tetrahydrobiopterin stimulates Ca2+ influx and growth hormone secretionin GH(3) cells and rat anterior pituitary cells

It has been reported that GR-tetrahydrobiopterin (GR-BH,) stimulated dopami ne release from rat striatum via cofactor activity-independent mechanisms, suggesting a novel action of BR-BH, at the cell membrane. We investigated t he effects of 6R-BH4 on Ca2+ influx, intracellular Ca2+ level ([Ca2+](i)) a nd growth hormone (GH) secretion in GH(3) cells and rat pituitary cells. 6R -BH4 elicited a dose-related increase in [Ca2+](i) levels in GH(3) cells de termined by fura-2 assay. 6R-BH4 acted on GH(3) cells to cause Ca-45(2+) up take, which was inhibited by nicardipine; and on GH(3) cells and rat anteri or pituitary cells to increase GH secretion, which was also inhibited by ni cardipine. In rat anterior pituitary cells, pretreatment with 2, 4-diamino- 6-hydroxypyrimidine, an inhibitor of de novo GR-BH, synthesis, inhibited CH secretion induced by GH-releasing hormone. These findings are compatible w ith a view that 6R-BH4 increases Ca2+ influx, elevates [Ca2+](i) and, in tu rn, releases GH in GH(3) cells and rat anterior pituitary cells; and give e xperimental bases that endogenous 6R-BH4 may play a role in GH secretion fr om the pituitary.