TY - JOUR
T1 - Enzymological studies of melanotropins
AU - Castrucci, Ana Maria de L.
AU - Hadley, Mac E.
AU - Sawyer, Tomi K.
AU - Hruby, Victor J.
N1 - Funding Information:
~-Melanotropin (ct-MSH), a tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2), is a hormone synthesized by the pars intermedia of the pituitary gland (Thody, 1980). A major role of this hormone is to control integumental color changes through its action on pigment cells within the skin. This hormone darkens the skins of many vertebrates by stimulating the centrifugal movements (dispersion) of melanosomes within melanocytes. MSH also affects mammalian melanocytes, both normal and abnormal (melanoma) cells, by activating adenylate cyclase, resulting in increased tyrosinase activity and melanogenesis (Bagnara and Hadley, 1973). ~-MSH, or a related melanotropin, may also be produced within the brain wherein it may function as a neurohormone in neural mechanisms related to learning and memory (O'Donohue and Dorsa, 1982). As a neurohormone (neurotransmitter or neuromodulator) ct-MSH may function importantly in thermoregulatory mechanisms (Glun and Lipton, 1981). In addition to the above actions, ct-MSH also may control many other systemic functions (Thody, 1980). Recently, several superpotent melanotropins were synthesized which exhibited prolonged effects on melanocytes, both in vivo and in vitro (Sawyer et al., 1980; Sawyer et al., 1982a). Two of these superagonists, \[Nle4 , D-Phe7\]-a-MSH and \[C~T,-,~st°\]-a-MSH, are commercially available as *Part of this work was supported by Public Health Service grants MH-27257, MH-30626, and AM-17420 and by grants PCM-883300, PCM-7707031, and PCM-810078 from the National Science Foundation. Dr. A. M. Castrucci is a fellow of the Conselho Nacional de Desenvolvimento Cientifico e Tecnolbgico of Brasil, grant 600/807/82.
PY - 1984
Y1 - 1984
N2 - 1. 1. The relative stability of natural melanotropins and related synthetic analogues to serum and purified proteolytic enzymes was studied. 2. 2. Both α- and β-MSH were rapidly inactivated by frog serum, but much more slowly by rat serum. β-MSH was more stable than α-MSH to serum inactivation. 3. 3. Both α- and β-MSH were rapidly inactivated by α-chymotrypsin and trypsin. 4. 4. The synthetic analogues, [Nle4, d-Phe7]-α-MSH and and [Cys4,Cys10]-α-MSH, were totally resistant to inactivation by frog and rat serum enzymes. 5. 5. [Nle4, d-Phe7]-α-MSH was resistant to inactivation by α-chymotrypsin and trypsin, whereas [Cys4,Cys10]-α-MSH, was partially resistant to these enzymes under similar conditions. 6. 6. Melanotropin analogues resistant to inactivation by serum enzymes may prove useful in a variety of physiological studies wherein natural melanotropins would be rapidly inactivated.
AB - 1. 1. The relative stability of natural melanotropins and related synthetic analogues to serum and purified proteolytic enzymes was studied. 2. 2. Both α- and β-MSH were rapidly inactivated by frog serum, but much more slowly by rat serum. β-MSH was more stable than α-MSH to serum inactivation. 3. 3. Both α- and β-MSH were rapidly inactivated by α-chymotrypsin and trypsin. 4. 4. The synthetic analogues, [Nle4, d-Phe7]-α-MSH and and [Cys4,Cys10]-α-MSH, were totally resistant to inactivation by frog and rat serum enzymes. 5. 5. [Nle4, d-Phe7]-α-MSH was resistant to inactivation by α-chymotrypsin and trypsin, whereas [Cys4,Cys10]-α-MSH, was partially resistant to these enzymes under similar conditions. 6. 6. Melanotropin analogues resistant to inactivation by serum enzymes may prove useful in a variety of physiological studies wherein natural melanotropins would be rapidly inactivated.
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U2 - 10.1016/0305-0491(84)90090-7
DO - 10.1016/0305-0491(84)90090-7
M3 - Article
C2 - 6332706
AN - SCOPUS:0021227377
SN - 0305-0491
VL - 78
SP - 519
EP - 524
JO - Comparative Biochemistry and Physiology -- Part B: Biochemistry and
JF - Comparative Biochemistry and Physiology -- Part B: Biochemistry and
IS - 3
ER -