alpha-Endorphin

Endorphins  are endogenous opioid peptides that function as neurotransmitters⁽¹⁾. They are produced by the pituitary gland and the hypothalamus in vertebrates during exercise, excitement, pain, consumption of spicy food, love and orgasm, and they resemble the opiates in their abilities to produce analgesia and a feeling of well-being.The term implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine⁽²⁾, Beta-endorphin (β-Endorphin) is released into blood from the pituitary gland and into the spinal cord and brain from hypothalamic neurons. The β-endorphin that is released into the blood cannot enter the brain in large quantities because of the blood–brain barrier, so the physiological importance of the β-endorphin that can be measured in the blood is far from clear. β-Endorphin is a cleavage product of pro-opiomelanocortin (POMC), which is also the precursor hormone for adrenocorticotrophic hormone (ACTH). The behavioural effects of β-endorphin are exerted by its actions in the brain and spinal cord, and it is presumed that the hypothalamic neurons are the major source of β-endorphin at these sites. In situations where the level of ACTH is increased (e.g., Cushing’s Syndrome), the level of endorphins also increases slightly⁽³⁾.

Figure1  Formula of a-Endorphin

Figure 2  mechanism of endorphin to inhibit LHRH release

Ref:

1. Oswald Steward: Functional neuroscience (2000), page 116.

2. Goldstein A, Lowery PJ (September 1975). "Effect of the opiate antagonist naloxone on body temperature in rats". Life Sciences 17 (6): 927–31.

3. Simantov R, Snyder S (1976). "Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor". Proc Natl Acad Sci USA 73 (7): 2515–9.

High-efficiency synthesis of human alpha-endorphin and magainin in the erythrocytes of transgenic mice: a production system for therapeutic peptides.[Pubmed:7937766]

Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9337-41.

Chemical synthesis of peptides, though feasible, is hindered by considerations of cost, purity, and efficiency of synthesizing longer chains. Here we describe a transgenic system for producing peptides of therapeutic interest as fusion proteins at low cost and high purity. Transgenic hemoglobin expression technology using the locus control region was employed to produce fusion hemoglobins in the erythrocytes of mice. The fusion hemoglobin contains the desired peptides as an extension at the C end of human alpha-globin. A protein cleavage site is inserted between the C end of the alpha-globin chain and the N-terminal residue of the desired peptide. The peptide is recovered after cleavage of the fusion protein with enzymes that recognize this cleavage signal as their substrate. Due to the selective compartmentalization of hemoglobin in the erythrocytes, purification of the fusion hemoglobin is easy and efficient. Because of its compact and highly ordered structure, the internal sites of hemoglobin are resistant to protease digestion and the desired peptide is efficiently released and recovered. The applicability of this approach was established by producing a 16-mer alpha-Endorphin peptide and a 26-mer magainin peptide in transgenic mice. Transgenic animals and their progeny expressing these fusion proteins remain health, even when the fusion protein is expressed at > 25% of the total hemoglobin in the erythrocytes. Additional applications and potential improvements of this methodology are discussed.

Construction of a quadroma to alpha-endorphin/horseradish peroxidase using an actinomycin D-resistant mouse myeloma cell line.[Pubmed:1358818]

Immunol Lett. 1992 Aug;33(3):217-22.

A hybrid hybridoma (quadroma), secreting antibodies with double specificity to alpha-Endorphin (alpha-EP) and horseradish peroxidase (HRP), has been produced. The bispecific antibodies constituted about 28-29% of all immunologically active IgG, produced by quadroma. The quadroma was isolated by fusion of two mouse hybridomas (anti-HRP and anti-alpha-EP) with distinct phenotypes: double mutant AMDR/HAT(S), and wild type (AMDS/HATR). A novel strategy for the construction of a double-mutant was applied, based on the use of an actinomycin D-resistant (AMDR) mouse myeloma for initiation of one of the parental hybridomas.

Isalpha-endorphin an uremic toxin?alpha-Endorphin isolated from filtrate of uremic patients with carbohydrate intolerance.[Pubmed:24190555]

Amino Acids. 1993 Feb;4(1-2):35-43.

A 16-residue peptide was isolated from filtrate of uremic patients with carbohydrate intolerance by ultrafiltration with an Amicon Centriflo DM-5 membrane, followed by gel-filtration on Sephadex G-50 and Sephadex G-25, droplet countercurrent chromatography and high performance liquid chromatography. The hexadecapeptide thus obtained was identical as the entire amino acid sequence ofalpha-Endorphin by amino acid analysis, application of the Edman degradation analysis and measurement of physical constants and analytical data of the synthetic hexadecapeptide. This result seems to suggest that an accumulation ofalpha-Endorphin in uremic patients might cause carbohydrate intolerance.

[The vagus-inhibiting action of alpha-endorphin].[Pubmed:1677295]

Biull Eksp Biol Med. 1991 Feb;111(2):174-5.

An intravenous bolus injection of 0.1 ml alpha-Endorphin (1 x 10(-8)-1 x 10(-4) g/ml) didn't change the heart rate in frogs. The parasympathetic bradycardia induced by the peripheral vagus stimulation was decreased by alpha-Endorphin. This vago-inhibitory action was dose-dependent (1 x 10(-5)-1 x 10(-4) g/ml). The maximal inhibitory action was watched in 4-8 and 9-15 minutes after bolus injection of alpha-Endorphin in concentration of 1 x 10(-5) and 1 x 10(-4) g/ml accordingly.