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We examined the role of endogenous tetrahydrobiopterin (BH 4 ) on L-tyrosine-induced increase in cytosolic Ca: concentration ([Ca 2+ ],) in the ß-cell line, HIT-T15. Addition of L-tyrosine to the cells increased [Ca 2+ ], in a conccntration- depcndent manner. Moreover, the L-tyrosine-induced [Ca 2+ ], elevation was blocked by L-3,4-dihydroxyphenylalanine (L-DOPA). Under low levels of BH 4  by treatment with 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH 4  biosynthesis, elevation of [Ca 2+ ], by L-tyrosine was stimulated. Moreover, co-prctreatment with sepiapterin, a precursor of BH 4  biosynthesis, reduced the decrease of BH 4  content by DAHP, and suppressed L-tyrosine-induccd [Ca 2+  ]¡ elevation in DAHP-pretreated cells. These findings suggest that BH 4  negatively regulates L-tyrosine-induced [Ca 2+ ] elevation via the production of L-DOPA in ß-cells.

Tetrahydrobiopterin Regulates L-tyrosine-induced Elevation of Cytosolic Calcium Concentration in Insulin-secreting Cells