Calcitonin receptor-stimulating peptide-1 regulates ion transport and growth of renal epithelial cell line LLC-PK1

Calcitonin receptor-stimulating peptide-1 (CRSP-1) is a peptide recently identified from porcine brain by monitoring the cAMP production through an endogenous calcitonin (CT) receptor in the renal epithelial cell line LLC-PK1. Here we investigated the effects of CRSP-1 on the ion transport and growth of LLC-PK1 cells. CRSP-1 inhibited the growth of LLC-PK1 cells with a higher potency than porcine CT. CRSP-1 enhanced the uptake of 22Na+ into LLC-PK1 cells more strongly than did CT and slightly reduced the 45Ca2+ uptake. The enhancement of the 22Na+ uptake was abolished by 5-(N-ethyl-N-isopropyl) amiloride, a strong Na+/H+ exchanger (NHE) inhibitor for NHE1, even at a concentration of 1 × 10−8 M, although other ion transporter inhibitors did not affect the 22Na+ uptake. These results indicate that CRSP-1 enhances the 22Na+ uptake by the specific activation of NHE1. Taken together, CRSP-1 is considered to be a new regulator for the urinary ion excretion and renal epithelial cell growth.