The minimal sequence of α-MSH required for full agonism on fish (Synbranchus marmoratus) melanocytes was determined to be Ac-α-MSH5-10-NH2 since Ac-α-MSH6-10-NH2 and Ac-α-MSH6-9-NH2 were inactive. The N-terminal tripeptide sequence, Ser-Tyr-Ser, lacked any contribution to potency since the 4-13 (Ac-[Nle4]-α-MSH4-13-NH2) sequence was equipotent to α-MSH. The important potentiating amino acids were found to be Met at position 4 of the amino terminus and Val at position 13 of the carboxy terminus of the hormone, since Ac-α-MSH4-10-NH2 was about 100 times more potent than the Ac-α-MSH5-10-NH2 sequence, and Ac-[Nle4]-α-MSH4-13-NH2 was about 10 times more active than Ac-[Nle4]-α-MSH4-12-NH2. The minimal sequence for equipotency to α-MSH was demonstrated to be Ac-[Nle4]-α-MSH4-13-NH2. [Nle4, d-Phe7]-α-MSH was about 10 times more active than α-MSH. Unexpectingly, several conformationally restricted cyclic melanotropins were either partial agonists ([Cys4, Cys10]-α-MSH) or totally inactive (Ac[Cys4, Cys10]-α-MSH4-10-NH2) on fish melanocytes. These results point out some rather remarkable differences between S. marmoratus and tetrapod melanophores relative to structural requirements for MSH receptor recognition and signal transduction.
ASJC Scopus subject areas
- Animal Science and Zoology