TY - JOUR
T1 - Melanin concentrating hormone analogues
T2 - Contraction of the cyclic structure. II. Antagonist activity
AU - Lebi, Michal
AU - Hruby, Victor J.
AU - Ana, Ana M.
AU - Hadley, Mac E.
N1 - Funding Information:
This work has been partially supported by grants from the US. Public Health Service (AM-17420, V.J.H.), the National science Foundation (DCB-86-15603, M.E.H.), and FAPESP 87/0851-4 and CNPq 407196/87, Brazil (A.M.C.).
PY - 1989
Y1 - 1989
N2 - 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 α-MSH, however, antagonized the melanosome aggregating actions of MCH on fish melanocytes. The antagonistic activity of the analogue, like that of α-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 α-MSH may be structurally and, therefore, evolutionarily related.
AB - 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 α-MSH, however, antagonized the melanosome aggregating actions of MCH on fish melanocytes. The antagonistic activity of the analogue, like that of α-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 α-MSH may be structurally and, therefore, evolutionarily related.
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U2 - 10.1016/0024-3205(89)90460-8
DO - 10.1016/0024-3205(89)90460-8
M3 - Article
C2 - 2784530
AN - SCOPUS:0024490127
SN - 0024-3205
VL - 44
SP - 451
EP - 457
JO - Life Sciences
JF - Life Sciences
IS - 7
ER -