Tyrphostin-23 enhances steroid-hormone secretion from dispersed human and rat adrenocortical cells

Tyrphostin-23 is commonly used as inhibitor of tyrosine kinase (TK). We fou nd that tyrphostin-23 concentration-dependently increased basal steroid-hor mone secretion from dispersed human and rat adrenocortical cells, the maxim al effective concentration being 10(-5) M. Tyrphostin-23 (10(-5) hi) enhanc ed 10(-9) M angiotensin-II- and endothelin-l -stimulated secretion of human and rat adrenocortical cells, but not the secretory response to 10(-9) M A CTH. However, it increased the response to lower concentrations (10(-12) or 10(-11) M) of ACTH. The secretagogue effect of tyrphostin-23 on dispersed rat adrenocortical cells was abolished by either the adenylate cyclase inhi bitor SQ-22536 (10(-4) M) or the protein kinase A (PKA) inhibitor H-89 (10( -5) M). Tyrphostin-23 (10(-5) M) raised basal cyclic-AMP release by dispers ed rat adrenocortical cells, but in the presence of the phosphodiesterase i nhibitor 3-isobutyl-1-methylxanthine (IBMX, 10(-3) M) it was ineffective. B oth tyrphostin-23 and IBMX increased cyclic-AMP release by rat adrenocortic al cells in response to 10(-10) M ACTH, and their effects were not additive . Taken together, our findings suggest that tyrphostin-23, acting as an inh ibitor of phosphodiesterases in adrenocortical cells, increases the intrace llular concentration of cyclic-AMP available for PKA activation thereby sti mulating steroid-hormone secretion. They also stress that caution must be u sed in interpreting the results of studies aimed at investigating the possi ble cross-talk between adenylate cyclase- and TK-dependent signaling cascad es.