|
| Product Name: | ALPHA-MSH | | Synonyms: | N-Ac-L-Ser-L-Tyr-L-Ser-L-Met-L-Glu-L-His-L-Phe-L-Arg-L-Trp-Gly-L-Lys-L-Pro-L-Val-NH2;α-Melanotropin【pig】;-Melanocyte-stimulating hormone;-Melanotropin, α;-MSH;α-MSH
Acetyl-ACTH (1-13) aMide, α-Melanotropin (huMan);Acetyl-ACTH (1-13) aMide, a-Melanotropin (huMan);Α-MELANOCYTE STIMULATING HORMONE ≥97% | | CAS: | 581-05-5 | | MF: | C77H109N21O19S | | MW: | 1664.88 | | EINECS: | 232-660-2 | | Product Categories: | Peptide Receptors;Melanocortin receptor;Peptide | | Mol File: | 581-05-5.mol |  |
| | ALPHA-MSH Chemical Properties |
| density | 1.48±0.1 g/cm3(Predicted) | | storage temp. | 2-8°C | | solubility | insoluble in EtOH; ≥10.44 mg/mL in H2O with ultrasonic; ≥166.5 mg/mL in DMSO with gentle warming | | pka | 4.43±0.10(Predicted) | | form | Lyophilized | | Water Solubility | Soluble in water (~1 mg/ml). | | BRN | 741840 |
| | ALPHA-MSH Usage And Synthesis |
| Synthesis and release | In rodents, α-MSH release is under strong inhibitory
control by direct innervation from hypothalamic neurons. Dopamine plays a role as a physiological melanotropin release-inhibiting hormone (MRIH). In contrast
to ACTH release from corticotropes in the pars distalis
of the pituitary, there is no apparent negative feedback
control on α-MSH release from melanotropes. Similar
mechanisms of regulation have also been demonstrated
in amphibians. In humans, the pars intermedia is functional in the fetus and neonate, whereas adults lack the
pars intermedia. | | Receptors | α-MSH and other MSH peptides interact with four of
the five subtypes of melanocortin receptors (MC1R,
MC3R, MC4R, and MC5R, excluding the ACTH-specific
receptor MC2R), which are members of the GPCR family.
Among them, MC1R is a classical α-MSH receptor. ACTH
interacts with all five MC receptors. α-MSH activates the AC/PKA pathway via
G proteins. | | Agonists and Antagonists | NDP-MSH and MT-II are agonists for human MC1R,
MC3R, MC4R, and MC5R. Kd for [125I]NDP-MSH:
0.33 nM (MC1R), 0.2 nM (MC3R), 4–1.2 nM (MC4R),
2.8 nM (MC5R). HS024 is an antagonist for human MC1R, MC3R,
MC4R, and MC5R. | | Clinical implications | The antiinflammatory activity of α-MSH includes
immunomodulatory effects on several resident skin cells
and antifibrogenic effects mediated via MC1R that are
expressed by dermal fibroblasts. In human mast cells,
α-MSH appears to be proinflammatory due to histamine
release. α-MSH exhibits cytoprotective activity against
ultraviolet B-induced apoptosis and DNA damage,
which is associated with the increased risk of cutaneous
melanoma in individuals with the loss of function
MC1R mutation. The congenital deficiency of POMC
results in a syndrome of hypoadrenalism, severe obesity,
and altered skin and hair pigmentation. In one case from
a Turkish family, a child who was homozygous for a
frameshift mutation in the N-terminal region of POMC,
and was thus predicted to have a loss of all POMC-derived peptides, showed typical symptoms of POMC
deficiency. However, this child did not have red hair,
unlike cases of Northern European origin. | | Biological functions | α-MSH and other MSH peptides
are associated with a wide spectrum of biological functions through MC receptors that distribute in many tissues. MC1R is expressed in melanocytes, keratinocytes,
macrophages, leukocytes, and adipose tissue; MC3R is
expressed in the central nervous system (CNS), kidney,
testis, ovary, skeletal muscle, placenta, and mammary
gland; MC4R is expressed in the CNS and associated with
food intake; and MC5R is expressed in exocrine glands,
muscle, and the CNS. The representative physiological
functions of MSH peptides mediated by MC receptors
are stimulation of melanocytes in the skin to synthesize
melanin, including regulation of the eumelaninpheomelanin switch via MC1R; energy homeostasis
and natriuresis via MC3R; energy homeostasis and erectile function via MC4R; and synthesis and secretion of
exocrine gland products via MC5R. | | Description | A pituitary hormone secreted from the pars intermedia,
MSH was one of the first adenohypophysial hormones
demonstrated to be present in vertebrates, from jawless fish
to mammals, together with adrenocorticotropic hormone
(ACTH). The fact that MSH is derived from a precursor protein
called proopiomelanocortin (POMC) was demonstrated
in 1979, using the pars intermedia from the bovine
pituitary. | | Uses | alpha-Melanocyte Stimulating Hormone amide is an endogenous melanocortin receptor agonist (Ki values are 0.12, 31, 660 and 5700 nM for MC1, MC3, MC4 and MC5 receptors respectively). Anti-inflammatory peptide; antagonizes proinflammatory mediators, including TNF-α, IL-6 and NO and induces anti-inflammatory cytokine IL-10. Inhibits food intake and induces penile erections following i.c.v. administration. | | General Description | α-Melanocyte-stimulating hormone (α-MSH) is a tridecapeptide, mostly produced by the cells in the brain, pituitary and circulation. Pro-inflammatory cytokines or UV light induced epidermal cells such as keratinocytes and melanocytes synthesize and discharge α–MSH. Poopiomelanocortin (POMC) acts as a precursor for α-Melanocyte-stimulating hormone (α-MSH) production. | | Biochem/physiol Actions | α-Melanocyte-stimulating hormone (α-MSH) acts as an anti-inflammatory agent via down regulating the production and activity of the pro-inflammatory cytokines interleukin-1 (IL-1), tumor necrosis factor (TNF)-α and IL-6 expressed in various cells of the immune system. It also controls the nitric oxide production associated with inflammation. α?MSH inhibits nuclear factor-κB (NF-κB)-dependent gene transcription and NF-κB pathway induced by TNF and other inflammatory agents. This activity of α-MSH is mediated through the production of cyclic adenosine monophosphate (cAMP) and activation of protein kinase A (PKA) enzyme. α–MSH functions as a potent therapeutics for various conditions resulted through NF-κB activation including, inflammatory diseases, human immunodeficiency virus (HIV) replication in AIDS (acquired immunodeficiency syndrome), and septic shock. α-MSH has an essential role to play in melanin production in animals. α-MSH regulates development of several skin diseases, including cutaneous inflammation and hyper-proliferative skin diseases. | | Clinical Use | The measurement of the blood concentration of MSH
has not been validated for routine clinical use. MSH analogs have recently been developed for antiobesity medication, treatment of skin diseases, and prevention of
actinic keratoses in organ transplant recipients. The
potential use of radiolabeled α-MSH peptides in melanoma imaging and the treatment of disseminated disease
has also been reported. | | storage | Store at -20°C | | Purification Methods | Its solubility in H2O is 1mg/mL. It is separated from the extract by ion-exchange on carboxymethyl cellulose, desalted, evaporated and lyophilised, then chromatographed on Sephadex G-25. [Lande et al. Biochemical Preparations 13 45 1971.] | | Structure and conformation | Three types of MSH molecules, with different amino
acid sequences, are contained in the common precursor
POMC in mammals. α-Melanocyte-stimulating hormone
(α-MSH) is composed of 13 aa residues. This peptide is generated from the N-terminal region of the adrenocorticotropic hormone (ACTH), and corresponds to acetylACTH(1–13)-amide. In MSH, the N-terminal Ser residue
is free, monoacetylated at the N position, or diacetylated
at the N and O positions, whereas the carboxyl terminal
is consistently in the amide form. These variations of
MSH are called desacetyl-α-MSH, α-MSH, and diacetyl-α-MSH, respectively. Of these peptides, α-MSH is a classical
α-MSH. β-MSH, which is generated from POMC via
β-lipotropin (β-LPH), is composed of 18 aa residues. Unlike
α-MSH, in β-MSH both termini are free. γ-MSH is produced
from POMC via pro-γ-MSH or N-POMC, which consists of
γ-MSH together with a joining peptide. γ-MSH (also known
as γ1-MSH) is composed of 12 aa residues in which the
N-terminus and the C-terminus are free and amide, respectively. γ3-MSH is composed of 25 aa residues in which the
N-terminal region corresponds to γ1-MSH. Each MSH segment is flanked by basic amino acid residues. Cartilaginous
fish such as sharks, rays, and ratfish possess δ-MSH in addition to the three other MSH peptides. Comparison with the
amino acid sequence and topology of POMC suggests that
δ-MSH might have evolved from β-MSH. Accordingly,
α-MSH and γ-MSH are suggested to share an antecedent.
Teleost POMC lacks γ-MSH.
 |
| | ALPHA-MSH Preparation Products And Raw materials |
|
