Relationships between calcium and chloride transport in frog skin glands

Frog skin gland, a furosemide-sensitive Cl(-)-secreting epithelium, exhibits Cl(-)-dependent Ca2+ secretion in response to stimulation by beta-adrenergic agonists. In this study, we further explored the relationships between Cl- and Ca2+ secretion in frog skin using 45Ca fluxes and short-circulating technique. On addition of isoproterenol (ISO) or 8-(p-chlorophenylthio)-cAMP, a significant positive correlation was demonstrated between Ca2+ secretion and Cl- secretion. Because Cl- transport in other Cl(-)-transporting epithelia may be modulated by prostaglandins or by changes in cytosolic Ca2+ activity, in addition to modulation by cAMP, we also examined the effects of prostaglandins (PG)E2 and F2 alpha, indomethacin (INDO), and the calcium ionophore A23187. Treatment with PGE2, PGF2 alpha, or A23187 at a dose of 10(-5) M resulted in marked stimulation in the amiloride-resistant short-circuit current, a reflection of Cl- secretion. This current was inhibited by furosemide addition or removal of Cl- from the bathing medium. However, and in contrast to stimulation with ISO or cAMP, PGE2, PGF2 alpha, and A23187 failed to induce Ca2+ secretion. In addition, the stimulation of Cl- secretion by A23187 was abolished by INDO (10(-6) M) pretreatment. Thus frog skin glands secrete Cl- via two mechanisms: one mediated by beta-adrenergic-cAMP stimulation and the other by activation of prostaglandin metabolism induced by changes in cytosolic Ca2+. Only the former pathway is associated with Ca2+ secretion. Furthermore, to account for the Cl- dependence of Ca2+ secretion, we postulate the existence of a Ca2+-Cl- cotransport system stimulated by cAMP.