Endorphins synthesis

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

Stress-related immune dysregulation also involves the synthesis of hormones including ACTH, growth hormone, and prolactin.14-17 Interestingly, it has also been demonstrated that various aspects of the immune response, for example., proliferation of B- and T-cells, cytokine production, antibody production, chemotaxis of monocytes and neutrophils, and natural killer (NK) cell cytotoxicity, can be affected by glucocorticoids (including cortisol) as well as peptides such as ACTH, CRH, endorphins, substance P, and somatostatin.1218... 

E Atherton, M Caviezel, H Fox, D Harkiss, H Over, RC Sheppard. Peptide synthesis. Part 3. Comparative solid-phase synthesis of human P-endorphin on polyamide supports using t-butoxycarbonyl and fluorenylmethoxycarbonyl. 

Vale A, Green S, Montgomery AM, Shall S (1998) The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test. J Psychopharmacol 12 268-272 Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41 -residue ovine hypothalamic peptide that stimulates secretion of corticotropin and p-endorphin. Science 213 1394-1397... 

Another example of processing of glycoproteins is found in the synthesis of pituitary hormones. ACTH, /3LPH, a-MSH, and /3-endorphin are synthesized from a common precursor in the neurointermediate lobe. Controlled, proteolytic cleavage liberates the final products, which are then secreted. Numerous other examples could be mentioned.3SS 393... 

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

A demonstration of liquid-phase combinatorial synthesis was recently introduced whereby the highly soluble, but highly crystalline, monomethyl polyethylene glycol (PEG) was employed to allow solution synthesis of a peptide library and solid phase-like purification by a change to a solvent where the PEG was insoluble. The demonstration penta-peptide library yielded the expected anti-P-endorphin binding sequence [65]... 

Many syntheses of 3-endorphin have been achieved in the past, either in solution or on solid-phase. For example, an A -Fmoc synthesis on solid-phase was reported by Atherton et al. (134). / -Alkoxybenzyl ester resin was selected as the solid support coupling was done by using the symmetric anhydride and HOBt active ester method, except that Asn and Ghi were coupled as / -nitrophenyl esters. The A"-Fmoc groups were deprotected by 20% piperidine in DMF. After completing the... 

Atherton E, Fox FI, Flarkiss D, Sheppard RC. Application of polyamide resins to polypeptide synthesis an improved synthesis of P-endorphin using fluorenyknethoxycarbonylamino-acids. J. Chem. Soc. Chem. Commun. 1978 13 539-540. 

Ling N. Solid-phase synthesis of porcine a-endorphin and y-endorphin, two hypothalamic-pituitary peptides with opiate activity. Biochem. Biophys. Res. Commun. 1977 74 248-255. 

In fact, a medley of substances (autacoids), kinins, prostaglandins, leukotrienes, histamine, endorphins, serotonin, vasopressin, has been implicated. In endotoxic shock, the toxin also induces synthesis of nitric oxide, the endogenous vasodilator, in several types of cells other than the endothelial cells which are normally its main source. 

Because ACTH synthesis originates from the POMC precursor peptide, its production by the pituitary is closely tied to the secretion of endogenous opiate peptides, such as P-endorphin. The physiological effects of endogenous opiates include (1) sedation, (2) an increased threshold of pain, and (3) autonomic regulation of respiration, blood pressure, and heart rate. These peptides are also involved in modifying endocrine responses to stress and water balance... 

In states of chronically elevated blood levels of insulin, there is a substantive decrease in the density of insulin receptors in insulin-dependent cells due to a decrease in the synthesis of insulin receptors. This phenomenon, which is referred to as downregulation, represents a means by which a cell autoregulates its receptivity to the hormone, and is also detected by other hormones such as the catecholamines, endorphins, and GnRH. The precise mechanisms involved in downregulation are not known. 

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