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.