Enkephalins endogenous

Opiates and opioid derivatives (a) delay the transit of intraluminal contents or (b) increase gut capacity, prolonging contact and absorption. Enkephalins, endogenous opioid substances, regulate fluid movement across the mucosa by stimulating absorptive processes. Limitations to the use of opiates include an addiction potential (a real concern with long-term use) and worsening of diarrhea in selected infectious diarrhea. 

All opiate derivatives are associated with constipation, but the degree of intestinal inhibitory effects seems to differ between agents. Orally administered opiates appear to have greater inhibitory effects than parenterally administered products. Orally administered enkephalins (endogenous opiate-like polypeptides) are recognized to have antimotility properties. 

Leu-enkephalin, Met-enkephalin [59141-40-11 polypeptide multiple tissues endogenous opiates... 

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). 

Enkephalins and Endorphins. Morphine (142), an alkaloid found in opium, was first isolated in the early nineteenth century and widely used in patent medicines of that eta. It is pharmacologically potent and includes analgesic and mood altering effects. Endogenous opiates, the enkephalins, endorphins, and dynotphins were identified in the mid-1970s (3,51) (see Opioids, endogenous). Enkephalins and endorphins ate Hsted in Table 9. 

Evidence soon emerged that the endogenous opioids were peptides rather than simple morphine-like molecules (9). The first direct evidence for endogenous opioids in brain extracts was provided in 1975 when two pentapeptides were purified that differed only in the carboxyl terminal amino acids (10) (Table 1). These peptides were called methionine- (Met-) and leucine- (Leu-) enkephalin, from the Greek term meaning "in the head."... 

Enkephalins belong to the group of endogenous opioid peptides. 

Endogenous ligand Endomorphin-1,-2 Met/leu-enkephalin Dynorphin A Nociceptin/OFQ... 

Three endogenous opioids have been identified enkephalins, dynorphins and beta-endorphins. These opioid peptides selectively bind to the seven transmembrane GPCRs delta (8), kappa (k), and mu (p). Although dynorphin binds predominately to the k receptor, P-endorphines and enkephalins bind to p and 8 opioid receptors. It is important to note that the analgesia induced by opioids is mediated predominately throngh the p opioid receptor. In vitro studies have shown a decrease in the immnne function and proliferation following p-endorphin administration in rodents (Ray and Cohn 1999) and that the immunosuppressive effects by P-endorphins are steroid-independent (Berkenbosch et al. 1984 Nelson et al. 2000). 

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... 

Endogenous opioid /i-endorphin Endomorphins Enkephalins Dynorphins Nociceptin... 

Since the discovery of the enkephalins in 1975 [11] a large number of endogenous opioid peptides have been detected in mammals, and at present three distinct families of opioid peptides are known (for a review, See Ref. 12). These are the enkephalins, the endorphins (a-, (J-, and y-), and the dynorphins and neoendorphins. The recently discovered endomor-phins [13] also may represent endogenous opioid peptides. Peptides with opioid activity have also been isolated from tryptic digests of milk casein... 

The identification of the morphine receptor spurred an effort in many laboratories to find an endogenous agonist for which that receptor was normally intended. Ultimately, a pair of pentapeptides that bound quite tightly to opiate receptors were isolated from mammalian brains. These peptides, called enkephalins (2, 3), show many of the activities of synthetic opiates in isolated organ systems. They do in fact show analgesic activity when injected directly into the brain. It is thought that lack of activity by other routes of administration is due to their rapid inactivation by peptide cleaving enzymes. 

Endorphins are found primarily in the limbic system, hypothalamus, and brainstem. Enkephalins and dynorphin (in smaller quantities) are found primarily in the periaqueductal gray matter (PAG) of the midbrain, the limbic system, and the hypothalamus. These endogenous substances mimic the effects of morphine and other opiate drugs at many points in the analgesic system, including in the dorsal horns of the spinal cord. 

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