Melanin concentrating hormone analogues: contraction of the cyclic structure. II. Antagonist activity.
Asp-Thr-Met-Arg-Cys-Met-Val-Gly-Arg-Val-Tyr-Arg-Pro-Cys-Trp-Glu-Val, melanin concentrating hormone (MCH), is a cyclic hormone possessing both MCH-like (melanin granule aggregating effect) and melanocyte stimulating hormone (MSH)-like (melanin granule dispersing effect) activities. Nine ring-contracted analogues were synthesized and characterized for their melanotropic activity on the fish (Synbranchus marmoratus) and frog (Rana pipiens) bioassays. In most cases, these analogues were totally devoid of MCH-like agonist activity, demonstrating the essential role of the disulfide bridge between residues 5 and 14 of the hormone. [Ala5, Cys10]MCH, for example, was totally devoid of MCH-like activity. This analogue, like alpha-MSH, however, antagonized the melanosome aggregating actions of MCH on fish melanocytes. The antagonistic activity of the analogue, like that of alpha-MSH, was Ca2+-dependent. Evidence suggested that this antagonism of MCH activity was related to the intrinsic MSH-like activity of the analogue. These results suggest that MCH and alpha-MSH may be structurally and, therefore, evolutionarily related.
Lebl
M
M
Department of Chemistry, University of Arizona, Tucson 85721.
Hruby
V J
VJ
Castrucci
A M
AM
Hadley
M E
ME
D000818:Animals; D002118:Calcium / Q000502:physiology; D005399:Fishes; D007028:Hypothalamic Hormones; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects; D010907:Pituitary Hormones / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011487:Protein Conformation; D011894:Rana pipiens
D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D009074:Melanocyte-Stimulating Hormones; D002118:Calcium