A-Dynorphin

Biosynthesis. Three separate genes encode the opioid peptides (see Fig. 1). Enkephalin is derived from preproenkephalin A, which contains six copies of Met-enkephalin and extended peptides, and one copy of Leu-enkephalin (62—66). ( -Endorphin is one of the many products of POMC, and represents the N-terminal 31 amino acids of P-Hpotropin (67,68). Three different dynorphin peptides are derived from the third opioid gene, preproenkephalin B, or preprodynorphin (69). The dynorphin peptides include dynorphin A, dynorphin B, and a-neo-endorphin. 

Preliminary data indicate that in the reserpinised rat or MPTP marmoset, the enkephalin agonist (SNC80) reduces PD-like symptoms without causing increased activity, i.e. no trend to dyskinesias. Enadoline, a dynorphin-like kappa opioid agonist also has similar effects in the same models. Whether it would be similar in humans remains to be seen. 

Leu3]enkephalin [Met3]enkephalin Dynorphin A Dynorphin B a-Neoendorphin (J-Neoendorphin ) Endorphin... 

Terasaki T, Hirai K, Sato H, Kang Y-S, Tsu-ji A (1989) Absorptive-mediated endocytosis of a dynorphin-like analgesic peptide, E2078, into blood-brain barrier. J Pharmacol Exp Ther 251 351-357... 

The p-, 5- and K-receptors have been cloned, and the first three show >50% identity. Subtypes and species-dependent variants within each of these receptors have been demonstrated, but there is >90% sequence homology. The recently cloned orphan receptor (ORL,) binds a dynorphin-like heptapeptide sequence. The physiological role of this... 

Reverses the agonist aetivity of Dyn A-(1-13)NH2 in an adenylyl cyclase assay using cloned k receptors, values against U50,488 and a dynorphin analog, respectively. 

Vincent SR, Hokfelt T, Christensson 1, Terenius L (1982b) Immunohistochemical evidence for a dynorphin immunoreactive striatonigral pathway. Eur. J. Pharmacol, 85, 251-252. 

Leu Jenkephalin [Met ] enkephalin Dynorphin A Dynorphin B A-Neoendorphin B-Neoendorphin Pij-Endorphin... 

The major opioid peptide derived from POMC is /5-endorphin. In addition to /5-endorphin, the POMC precursor also is processed into the nonopioid peptides adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormone (a-MSH), and /5-lipotropin /5-LPH). Proenkephahn contains multiple copies of met-enkephalin, as well as a single copy of leu-enkephalin. Prodynor-phin contains three peptides of differing lengths that aU begin with the leu-enkephalin sequence dynorphin A, dynorphin B, and neoendorphin (Eigure 21-1). 

Figure 33 Cleavage of pro-opiomelanocortin (POMC) into endorphin and non-opioid peptides. POMC serves as a precursor (pro-) for the opiate peptide, -endorphin (-opio-) for a-, J3- and y-melanocyte-stimulating hormone (MSH, -melano-) for adrenocortkotrophic hormone (ACTH, -cort-) and for a- and /3- lipotropin (-in). Notice that the peptides are not located end-to-end, but that some of the smaller peptide sequences are embedded in larger sequences (e.g., a-lipotropin, P-MSH and P-endorphin are contained within P-lipotropin). Two other protein precursors contain enkephalins and dynorphins. Proenkephalin contains seven met-enkephalin sequences (Tyr-Gly-Gly-Phe-Met). Prodynorphin contains three leu-enkephalin sequences (Tyr-Gly-Gly-Phe-Leu) and the sequences for dynorphin A, Dynorphin B, a-neodynorphin and P-neoendorphin.

Glu25-Glu -Leu -Phe2 -Asp2 -VaP-COO-Fig. 2 Sequences of (a) dynorphin A and (b) dynorphin B... 

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