Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla

Abstract

Biologically active peptide hormones and neurotransmitters have been shown to be enzymatically liberated from larger, inactive precursor molecules by tissue-specific post-translational processing, particularly at the typical cleavage signals of paired basic residues^1,2. Subsequent N-terminal or C-terminal modifications may be of importance in regulating the biological activities of these peptides (for review see ref. 3). C-terminal α-amidation is considered to be essential for the biological function of several non opioid peptides^4,5. Here we present the isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla. Amidorphin and the recently isolated octapeptide metorphamide⁶ (adrenorphin⁷) are the only endogenous opioid peptides in mammals known to possess a C-terminal amide group. The amino acid sequence of amidorphin corresponds to the sequence 104–129 of bovine proenkephalin A (refs 8, 9). Very high concentrations of amidorphin were detected in bovine adrenal medulla and in a further endocrinological system, the hypothalamic–neurohypophyseal axis. Amidorphin may there fore be considered to be a major gene product of the opioid peptide precursor proenkephalin A in these endocrine tissues.