Stimulation of the adenylate cyclase of A B16 melanoma cell line by pro-opiocortin-related peptides--a structure-activity study.
The ability of alpha-melanotrophin (alpha-MSH or ACTH 1-acetyl-13 amide) and other structurally related peptides derived from the common precursor, pro-opiocortin, to stimulate adenylate cyclase activity in a pigmented B16 mouse melanoma was investigated. The peptides ACTH 1-39, ACTH 1-24, alpha-MSH, ACTH 1-13 amide and beta-MSH all stimulated the enzyme to a similar maximal extent and with similar potency (ED50 = 1.3 . 10(-6) M) except that ACTH 1-39 was slightly less potent (ED50 = 5 . 10(-6) M). ACTH 4-10 (ED50 = 4 . 10(-5) M) and gamma-MSH (ED50 = 5 . 10(-6) M) were partial agonists. ACTH 1-10 was no more effective than ACTH 4-10 in stimulating the enzyme whereas ACTH 1-13 amide was a full agonist. The peptides beta-endorphin and its derivatives, Met-enkephalin and melanotrophin potentiating factor (MPF), failed to stimulate the enzyme. We suggest that the B16 melanoma requires not only the sequence ACTH 4-10 but also some part of the sequence ACTH 11-13, or a similar sequence in the terminal portion of beta-MSH, for full activation of the receptor-linked enzyme.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003366:Cosyntropin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008545:Melanoma / Q000201:enzymology*; D000090204:Mesothelin; D051379:Mice; D009374:Neoplasms, Experimental / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000031:analogs & derivatives*
C000715528:Msln protein, mouse; D010446:Peptide Fragments; D003366:Cosyntropin; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D000262:Adenylyl Cyclases; D000090204:Mesothelin