Neuropeptide K-(1-24)-peptide: Storage and release by carcinoid tumors

An antiserum directed against the COOH-terminal region of neuropeptide K-(1-24)-peptide that shows only 0.5% reactivity with neuropeptide K has been used in radioimmunoassay to study the posttranslation processing of human β-preprotachykinin. A primary midgut carcinoid tumor contained high concentration of substance P (2970 pmol/g), neurokinin A (3660 pmol/g) and neuropeptide K-(1-24)-peptide (3430 pmol/g) but only a very low concentration (<5 pmol/g) of intact neuropeptide K. Neuropeptide K-(1-24)-peptide was also detected in extracts of metastatic tumor tissue from four patients with midgut carcinoid tumors. The amino acid sequence of tumor neuropeptide K-(1-24)-peptide was identical to that predicted from the nucleotide sequence of a human β-preprotachykinin cDNA. The fasting plasma concentration of neuropeptide K-(1-24)-peptide was elevated in a patient with the carcinoid syndrome (821 fmol/ml compared with <18 fmol/ml in healthy subjects) and rose approximately 2-fold after intravenous pentagastrin. The study has demonstrated that the Lys²⁵-Arg²⁶ bond in neuropeptide K (corresponding to Lys⁹⁶-Arg⁹⁷ in the precursor) is an important processing site in human β-preprotachykinin.