Endorphins, role

Dynorphin may also influence nociception at the spinal level. The levels of prodynorphin mRNA and immunoreactive dynorphin increase in the chronic inflammatory arthritic model (158). Dynorphin also inhibits morphine or P-endorphin-induced analgesia in naive animals and enhances analgesia in tolerant animals, indicating that this peptide may have a regulatory role in opioid analgesia (159). This effect does not appear to be mediated by a classical opioid receptor, since des-tyrosine dynorphin, which does not bind to opioid receptors, also antagonizes morphine analgesia (160). 

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... 

Signals from pain receptors are transmitted to the brain where they are processed in the thalamus and then passed on to the sensory cortex where the sensation of pain originates. Receptors for endorphins (and for the opiates) are abundant in these regions and it is likely that a natural role of endorphins is to interfere with the transmission of impulses through these regions. The opiates appear to do the same, acting not so much to alter the pain threshold but altering the patient s attitude to pain. 

Hydroxytryptamine (5-HT), dopamine, and norepinephrine play important roles as central neurotrans-mitters in the process of erection. Still other substances or hormones, such as endorphins, oxytocin, vasopressin, adrenocorticotropic hormone (ACTH) and related peptides, and prolactin, appear to participate in the complex and coordinated process of penile erection. Central nonadrenergic neurons also may influence male sexual behavior. 

Additionally, an opioid antagonist, naltrexone, has been used to treat children with autism. The results from these studies have been mixed, with some studies showing a mild decrease in hyperactivity and self-injurious behavior, and improved attention (Gillberg, 1995). The children who respond best to this medication appear to have more severe abnormalities in their beta endorphin levels (Bouvard et al., 1995). Overall, the research suggests that the endogenous opioid system, which is important in the reward aspects of affiliation, may also play a role in the neurobiology of autism. 

Benton, D. and Brain, P.F. (1988) The role of opioid mechanisms in social Interaction and attachment. In Rodgers, R.J. and Cooper, S.J., eds. Endorphins, Opiates and Behavioural Processes. New York John Wiley Sons, pp. 215-235. 

Opiates act on a variety of receptors. The three most important subtypes are the mu, delta, and kappa opiate receptors (Fig. 13—25). The brain makes its own endogenous opiate-like substances, sometimes referred to as the brain s own morphine. They are peptides derived from precursor proteins called pro-opiomelanocortin (POMC), proenkephalin, and prodynorphin. Parts of these precursor proteins are cleaved off to form endorphins or enkephalins, stored in opiate neurons, and presumably released during neurotransmission to mediate endogenous opiate-like actions (Fig. 13-25). However, the precise number and function of endogenous opiates and their receptors and their role in pain relief and other central nervous system (CNS) actions remain largely unknown. 

Taylor, Kaiser, and their co-workers (Taylor and Kaiser, 1986) prepared a series of model peptides that were designed to test the role of each of the postulated modules in /8-endorphin. Figure 13 illustrates a-helical net diagrams of the proposed helical auxiliary sequence of /3-endorphin. The hydrophobic residues in this structure cover half the surface of the helix, twisting around the structure in a clockwise manner. [It has also been noted that if this sequence were to form a tt helix rather than an a... 

Lin-Liu, S. Bawin, S. M. Adey, W. R. Role of 8-endorphin on calcium effluxes in synaptosomes. Society for Neuroscience, Annual Meeting, Cincinnati, Ohio, November 1980. Proceedings, p. 766 (Abstract No. 260.5). 

SP, which can function as a neurotransmitter in various brain regions, suppresses the action of morphine and endorphins and is thought to play a protective role against stress-determined disturbances. 

The morphinomimetic peptides react with the same receptors as the opiate alkaloids and presumably represent the endogenous agonists of these receptors. /i-Endorphin, which represents the functionally active molecule, plays a role in the response of the organism to stress stimuli. The analgesic effect in the body can be traced back to the secretion of /1-endorphin. Accordingly, acupuncture, for example, activates the central nervous endorphin system and causes an increase in the endorphin concentration, leading to the elimination of sensitivity to pain. Presumably there are endorphinergic systems in the central nervous system (CNS) in which the endorphins assume a neuro-modulatory function. 

A variety of chemically-identified neurons within the ARC receive both indirect (extrinsic) and direct (intrinsic) enkephalinergic neuronal input (Magoul et al., 1993) suggesting a role for enkephalin in the neuroendocrine regulation of pituitary hormone secretion. Enkephalin-IR perikarya in the bed nucleus of the stria terminalis, medial preoptic nucleus, periventricular nucleus and dorsomedial nucleus all provide extrinsic input to the rostral ARC, whereas intrinsic enkephalin neurons connect the rostral and caudal portions of the ARC (Magoul et al., 1993). Enkephalin-IR neurons innervate TH-IR neurons (perikarya and dendrites) in the DM-ARC (but not in the VL-ARC), (5-endorphin neurons in the VL-ARC, and NPY neurons in the ventromedial ARC (Magoul et al., 1994). There are symmetrical synaptic connections between enkephalin axon terminals and POMC perikarya in the ARC (Zhang et al., 1987), and reciprocal synaptic associations with NPY neurons in the ventromedial ARC (Li et al., 1993). 

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