Removal of Arg1 and Phe22 from CLIP (ACTH18-39) by rodent pituitary and blood peptidases.

The major product on incubation of CLIP (ACTH18-39) with rat and mouse serum, rat plasma and whole blood, and soluble extracts of rat pituitary is [des-Arg1]-CLIP (ACTH19-39) while [des-Phe22]-CLIP (ACTH18-38) is the major product with pituitary particulate fraction. In both cases, p-chloromercuribenzoate-sensitive, metal-dependent peptidase activity appears to be responsible for the cleavage. The serum enzyme may be related to proline aminopeptidase. Material coeluting with [des-Arg]-CLIP on two HPLC solvent gradients is present in the superfusion media from neurointermediate lobes of genetically obese (ob/ob) mice but is not present in acid extracts of the lobe. This suggests that postsecretory processing of CLIP may involve removal of the N-terminal Arg residue.