JS-Endorphin

The opioid receptors are for the endogenous opioids, peptide transmitters, jS-endorphin, endomorphins, enkephalins, dynorphins and nociceptin. Thus all the problems of drugs based on peptides need to be overcome in order for the roles of these... 

High doses of caffeine produce a stresslike neuroendocrine response (Spindel 1984 Spindel et al. 1984). This includes increased levels of corticosterone, jS-endorphin, and decreased serum growth hormone and thyrotropin-stimulating hormone in the rat. However, similar effects are not observed in humans until approximately 500 mg is consumed, the equivalent of 5 cups of coffee. At this dose in humans, elevations are seen in adrenocorticotrophic hormone, jS-endorphin, and cortisol. 

The inverse relationship between dopamine and the jS-endorphin neurons is of fundamental evolutionary significance. It is the final common pathway for inhibition of estrus during pregnancy and lactation, nature s own means of contraception. ... 

Fic. 16. Chromatographic profiles of the tryptic digest peptides from rat and camel jS-endorphin. Chromatographic conditions column, 10-/xm LiChrosorb RP18 (25 x 0.32 cm) eluent, 1 M pyridine-0.5 M acetic acid primary buffer with a lOO-min linear gradient of rt-propanol from 0 to 20% flow rate, 14 ml/h. (A) Mixture of trypsin digested rat (150 pmol) and camel (250 pmol) /3-endorphin (B) rat (150 pmol) tryptic peptides (C) camel (250 pmol) tryptic peptides. Reprinted with permission from Rubinstein et al. (77). Copyright by Academic Press, Inc., New York. 

Members of class H include jS-endorphin (Taylor and Kaiser, 1986), calcitonin (Epand et al., 1983), secretin (Robinson etal., 1982), glucagon (Wu and Yang, 1980), and adrenocorticotropic hormone (Verhallen el al., 1984). Peptides of this structural class average 36 residues in length, with the longest member being the 84-residue parathyroid hormone (Epand et al., 1985). The helical domains make up only a portion of these peptides, often inset several residues from the N terminus, and cover approximately 18-20 residues. 

Fentanyl stimulates mu-opioid receptors in the central nervous system (CNS), altering the body s response to pain. Fentanyl may alter the release of different neurotransmitters, such as jS-endorphin, sensitive to pain. Fentanyl can produce profound CNS and respiratory depression through mechanisms common to other opioids. Respiratory depression is mediated through action on the medullary respiratory center. Fentanyl is 50-100 times more potent... 

The classical mammalian opioid peptides are derived from three distinct precursor proteins (Fig. 7.10) (see Refs. 75,266 for reviews). Processing of the precursor proteins occurs at pairs of basic residues. jS-Endorphin is derived from proopiomelanocortin (POMC), along with ACTH, a-MSH, and j3-lipotropin (see Ref 267 for a review). The enkephalins are derived from proenkephalin A (see Ref 268 for a review). This protein contains four copies of Met-enkephalin flanked by pairs of basic resi-... 

Some polyproteins are differentially cleaved in different tissues. An example is proopiomelanocortin, a polyprotein that is the source of several hormones synthesized in the pituitary gland. In the anterior lobe of the pituitary, the polyprotein is cleaved to release -lipotropin and adrenocorticotropic hormone (ACTH). In the intermediate lobe, a different pattern of cleavage forms jS-endorphin and a-melanotropin (Chapter 31). 

Fig. 9. Plot of CTv jxp/ v.caio versus 1/b for the jS-endorphin-related polypeptides 1-6 (Table.2). Data acquired under conditions of different gradient time Iq = 20, 30, 40, 60 and 120 min, with the same mobile phase composition limits (water containing 0.1% TFA to water-acetonitrile (50 50) containing 0.1% TFA) at a constant flow rate of 1 ml/min. Column, developmental C,g, dp = 6 /im, pj = 15 nm, 25 cmX4.6 mm ID. The value of Ov aic was calculated from (a) Cv.caic [

The example of the opioid peptides in rat pituitary (Rubinstein et ai, 1977a,b) will be used to demonstrate this application. The molecular weights of jS-lipotropin and jS-endorphin, which had been isolated from rat pituitaries, were shown to correspond to the values of the same peptides from sheep. To achieve maximal sensitivity all of the effluent from a Bio-Gel P-30 column was directed to fluorescence detection. The Bio-Gel P-30 column had been calibrated with 20-pmol samples of known linear peptides (having no disulfide bonds). 

Amino acid analyses were performed on an instrument with a fluores-camine detection system. Individual samples, containing 50-100 pmol of peptide, were hydrolyzed and analyzed. Rat )8-lipotropin was found to be similar in composition, especially with respect to the basic amino acids, to sheep jS-lipotropin. Rat j8-endorphin was shown to be identical in composition to sheep jS-endorphin. 

Chromatography of mixture of the peptides insulin chain A (1), insulin chain B (3) and jS-endorphin fragments 1-27 (2) from pNIPAM-BMA-modified column (BMA 5%, eluent 0.9% NaCI aqueous solution). (Source Reproduced from Kanazawa and Okano (2011).Temperature-responsive chromatography for the separation of biomolecules. Journal of Chromatography A, 1218, 8738-8747. Copyright (2011), with permission from Elsevier.) (Kanazawa and Okano, 2011). 

Ali SF, Hong JS, Wilson WE, et al. 1982. Subchronic dietary exposure of rats to chlordecone (Kepone ) modifies levels of hypothalmic -endorphin. Neurotoxicology 3(2) 119-124. 

Hong JS, AN SF. 1982. Chlordecone (Kepone) exposure in the neonate selectively alters brain and pituitary endorphin levels in prepuberal and adult rats. Neurotoxicology 3(2) 111-117. 

As recorded above, the enkephalins have been found to be derived from larger precursors. /3-Endorphin is derived from the pituitary hormone fi-lipotropin which contains 91 amino acid residues and stimulates the release of fatty acids from adipose tissues. jS-Lipotropin is, in turn, derived from the even larger precursor proopiocortin which contains 265 residues. 

Fig. 1.8. The organization of a multicomponent precursor synthesized in the pituitary and yielding by cleavage different hormones (according to Tata, 1978 Roberts and Herbert, 1977a,b Roberts et al, 1978). This precursor molecule has a molecular weight of 31,000 and is composed of about 260 amino acids. The hormone ACTH has 39 amino adds and is released by proteolytic cleavage of the N-terminal end further cleavage of ACTH gives peptide 1-13 which is a-MSH. jS-Lipotropin is formed by 91 amino adds in C-terminal position it contains jJ-MSH, endorphins and enkephalins which are also obtained by proteolytic cleavage. Peptide 61-76 is the a-endorphin 61-77 the y-endorphin 61-91 which represents the C-terminal fragment is the / -endorphin and 61-65 is the Met-enkephalin (from Tata, 1978).

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