Natural opioid peptides

The effects of synthetic and natural opioid peptides in isolated organs Ronai, A. Z. Berzetei, I. Szekely, J. I. Bajusz, S. 

Endogenous opioid peptides are the wide variety of endogenous peptides isolated since 1975 which are the natural ligands for the opioid receptors. The peptides... 

Lord, J. Waterfield, A. Hughes, J. and Kosterlitz, H.W. Endogenous opioid peptides Multiple agonists and receptors. Nature (London) 267 495-500, 1977. 

Erspamer Y, Melchiorri P, Falconieri-Erspamer G, et al. Deltorphins a family of naturally occurring peptides with high affinity and selectivity for opioid binding sites. Proc Natl Acad Sci USA 1989 86 5188-5192. 

Lord J, Waterfield A, Hughes J et al. Endogenous opioid peptides multiple agonists and receptors. Nature 1977 267 495-498. 

Weisskopf M, Zalutsky R, Nicoll RA. The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation. Nature 1993 365 188-190. 

A series of peptides, occurring naturally in brain and possessing pharmacological properties similar to those of morphine, have been described. At least three separate families of peptides have opioid properties (Table 24.2), and the different classes of peptides reside in separate distinct neurons. It is likely that the endogenous opioid peptides coexist in neurons with other nonopioid neurotransmitters. The initial hope that these endogenous agents or synthetic derivatives of them would be found to retain the analgesic activity of the opioids but be devoid of respiratory depression and/or addictive properties has now somewhat abated. 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

The third group consists of naturally occurring and synthetic peptides with opioid-like properties. The opioid peptides were discovered during the search for endogenous ligands of the opioid receptors and share the same action and side-effect profile as the non-peptidic compounds... 

Endogenous opioid peptides. Extensive processing is also involved in formation of analgesic opioid peptides, which are present naturally in the brain (see also Section B). Tire formation of (1-endorphin in the hypothalamus from prepro-opiomelanocortin (Fig. 30-2) has already been mentioned. Prior to the discovery of P-endorphin, the pentapeptides Met-enkephalin and Leu-enkephalin (Table 30-4) were discovered and were found to compete with opiate drugs for receptors in the brain. Tire larger P-endorphin, which contains the Met-enkephalin sequence at its N terminus, is a far more potent opiate antagonist than are the enkephalins. Since the Met-enkephalin sequence within P-endorphin is not flanked by basic residues, it apparently is normally not released. Two other recently discovered brain peptides are endomorphin-1 (YPWF-NH2) and endomorphin-2 (YPFF-NH2). They are also potent agonists for the opioid receptors, especially the p receptor (see Section B,10).,61a,61b... 

Fentanyl and its derivatives are opioid narcotics similar to heroin and are consumed on the street in many of the same ways. These opioids work through receptors in the brain and spine, mimicking naturally present peptides commonly known as endorphins, enkephalins, and dynorphins. The type of receptor that fentanyl predominately bonds with is the mu receptor. 

In addition to the opioid peptides which occur in the mammalian brain, it is now evident that morphine, codeine and related benzomorphans occur naturally, in trace amounts, in the brain, where they exist in a conjugated form usually bound to brain proteins. The significance of these substances to brain function is unclear. 

A unique characteristic of amphibian opioid peptides is the presence in the second N-terminal position of a D-amino acid residue that confers to these compounds high resistance against enzyme degradation. Hence amphibian opioids, unique among naturally occurring opioid peptides, can act centrally after peripheral administration. 

The transient nature of the pharmacological actions of the enkephalins was noted early in opioid peptide studies, a fact that was soon correlated with... 

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