Calcitonin (CT) is a polypeptide hormone and has a variety of functions including regulation of urinary calcium excretion. By using a cDNA subtraction hybridization method, we identified that N-F-IL3A and urokinase-type plasminogen activator (uPA) genes were up-regulated by CT in porcine renal cell line LLC-PK1. CT-mediated induction of these genes was not inhibited by cycloheximide. These data suggest that these up-regulations are not induced by increased synthesis of regulating proteins; therefore, they are immediately response early (IE). We also found that CT treatment led to the phosphorylation of Erk1/2. We demonstrated that PD98059, a MEK1 inhibitor, inhibited CT-induced mRNA expressions of uPA, but had no obvious influence on the NF-IL3A induction. These results demonstrated the inductions of uPA by CT involve Erk1/2 phosphorylation. We provide the first evidence that NF-IL3A expression is upregulated by CT. The present findings suggest that the transcriptions of the NF-IL3A and uPA could be induced by CT and might be important mediators of CT function in renal cells. (C) 2002 Elsevier Science (USA).