Opioids precursor

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... 

Stefano GB, Salzet M. Invertebrate opioid precursors evolutionary conservation and the significance of enzymatic processing. Int Rev Cytol 1999 187 261-286. 

The second application of the CFTI approach described here involves calculations of the free energy differences between conformers of the linear form of the opioid pentapeptide DPDPE in aqueous solution [9, 10]. DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen, where D-Pen is the D isomer of /3,/3-dimethylcysteine) and other opioids are an interesting class of biologically active peptides which exhibit a strong correlation between conformation and affinity and selectivity for different receptors. The cyclic form of DPDPE contains a disulfide bond constraint, and is a highly specific S opioid [llj. Our simulations provide information on the cost of pre-organizing the linear peptide from its stable solution structure to a cyclic-like precursor for disulfide bond formation. Such... 

In the anterior pituitary gland (see Hormones, anteriorpituitaryhormones), both adrenocorticotropic hormones (ACTH) and the endogenous opiate hormone, P-endorphin, are synthesized from a common prohormone (2) (see Opioids,endogenous). In the adrenal medulla, five to seven copies of another opiate hormone, methionine—enkephalin (Met-enkephalin), and one copy of leucine—enkephalin (Leu-enkephalin) are synthesized from each precursor molecule (3). 

Fig. 2. Schematic drawing of the precursors for opioid peptides. Shaded areas represent the location of sequences of active peptide products which are normally released by trypsin-like enzymes acting on pairs of basic amino acid residues. Precursors are not necessarily drawn to scale.

GUal precursors in the ventricular and subventricular zones can also express opioid receptors (Zhu et al. 1998 Reznikov et al. 1999 Stiene-Martin et al. 2001 Kim et al. 2006 Tripathi et al. 2008). Immature glia and adult progenitors express opioid receptors, which affect ceUular maturation (Stiene-Martin and Hauser 1990, 1991 Stiene-Martin et al. 1991 Persson et al. 2003,2006) and cell fate decisions (Kim et al. 2006). Importantly, gUal precursors (Khurdayan et al. 2004 Lawrence et al. 2004 Buch et al. 2007), and espedaUy immature oUgodendroglia (Khurdayan et al. 2004 Hauser et al. 2008), also appear to be vulnerable to opioids and HIV-1 proteins. 

Khurdayan VK, Buch S, El-Hage N, Lutz SE, Goebel SM, Singh IN, Knapp PE, Turchan-Cholewo J, Nath A, Hauser KF (2004) Preferential vulnerabihty of astroglia and glial precursors to combined opioid and HlV-1 Tat exposure in vitro. Eur J Neurosci 19 3171-3182... 

The classic endogenous opioid peptides are derived from one of three families of precursors proopiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. Many active opioid peptides are derived from these three, but the best known are )S-endorphin, enkephalin, and dynorphin. POMC is produced by nuclei in the hypothalamus and medulla (Khachaturian et al. 1985 Watson et al. 1978 Bloom et al. 1978). Enkephalin and dynorphin neurons are distributed to all levels of the central nervous system (Hokfelt et al. 1977 Khachaturian et al. 1983 Sar et al. 1978 Khachaturian et al. 1985). 

Endogenous opioids are peptides that are cleaved from the precursors proenkephalin, pro-opiomelanocortin, and prodynorphin. All contain the amino acid sequence of the pentapeptides [Met]- or [Leuj-enkephalin (A). The effects of the opioids can be abolished by antagonists (e.g., naloxone A), with the exception of buprenorphine. 

Opioid receptors and their precursor mRNAs are distributed throughout the brain and spinal cord. High levels of opioid binding have been found in the ascending pathways for nociceptive transmission, including the... 

Endogenous opioid peptides are derived from three distinct precursor molecules, which are the primary products of three separate genes (Simon and Hiller,... 

In a further application of a ring-closing metathesis, the preparation of the syn- and A -azepinones 169 and 170, respectively, was achieved from the hydrochloride salt of the precursor 168 using Grubbs I catalyst (Equation 19). The jy -isomer 169 showed particularly strong (subnanomolar) in vitro binding to the K-opioid receptor <2004BML5693>. 

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