Regulation of epithelial sodium channel activity in A6 cells via the peptide hormone, prolactin (1181.9)

Abstract

Prolactin (PRL) is a peptide hormone well‐known for its role in lactation. PRL also has osmoregulatory actions via alteration of ion and water transport, actions characterized mostly in aquatic life. In 2003, researchers reported that PRL stimulates epithelial sodium channel (ENaC) activity in adult frog skin. Since that time, PRL‐mediated regulation of ENaC has been largely ignored. Given that ENaC present in the kidney plays an essential part in blood pressure control, we hypothesized that PRL may control blood volume and blood pressure via regulation of ENaC activity. To investigate this hypothesis, we used a well‐known frog kidney cell model (A6‐2F3) possessing amiloride‐sensitive transepithelial current and highly selective sodium channels with a conductance of ~5pS. Amiloride‐sensitive (ENaC‐mediated) current dramatically increased within 30 minutes after application of 1µg/mL PRL to the basal side of the cells ‐ an effect sustained even at 24 hours after treatment. We confirmed this finding using cell attached patch clamp. We found an almost 6 fold increase in ENaC NPo in PRL‐treated versus vehicle‐treated cells. The mechanism, although still not clear, at least partially involves JAK2 signaling since AG‐490, a JAK2 inhibitor, reduced the effect of PRL on amiloride‐sensitive current in A6 cells. Inhibitors of PI3K and SRC had no effect on PRL’s induction of amiloride‐sensitive current. In conclusion, we observed a significant induction of ENaC activity in frog kidney cells exposed to PRL ‐ an effect partially mediated through JAK signaling pathways. Future studies will finalize the signaling mechanisms involved in PRL’s activation of ENaC and the role of these pathways in blood pressure control.Grant Funding Source: Supported by NIH K12GM000680 and T32HL076118