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

Abstract

We examined the role of endogenous tetrahydrobiopterin (BH4) on L-tyrosine-induced increase in cytosolic Ca: concentration ([Ca2+],) in the ß-cell line, HIT-T15. Addition of L-tyrosine to the cells increased [Ca2+], in a conccntration- depcndent manner. Moreover, the L-tyrosine-induced [Ca2+], elevation was blocked by L-3,4-dihydroxyphenylalanine (L-DOPA). Under low levels of BH4 by treatment with 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 biosynthesis, elevation of [Ca2+], by L-tyrosine was stimulated. Moreover, co-prctreatment with sepiapterin, a precursor of BH4 biosynthesis, reduced the decrease of BH4 content by DAHP, and suppressed L-tyrosine-induccd [Ca2+ ]¡ elevation in DAHP-pretreated cells. These findings suggest that BH4 negatively regulates L-tyrosine-induced [Ca2+] elevation via the production of L-DOPA in ß-cells.

Keywords

• tetrahydrobiopterin
• calcium
• l-tyrosinc
• ß-cell