P-endorphin release

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

There is still a great deal of uncertainty regarding the actual role that immunity plays in the control of human malignancy [76-79]. Until this point is settled, the role of immunostimulating mistletoe extracts will also remain open. Nevertheless, the immunosuppression that accompanies tumor development affects the patient, at least indirectly, by the predisposition to infections. It complicates the treatment and can be a major cause of mortality (e. g. in multiple myeloma patients). How to cope with opportunistic infections seems worth investigating since positive results might have therapeutic implications. Further, it has been reported that mistletoe treatment may improve the life quality of cancer patients by inducing p-endorphin release [80]. 

Heiny BM, Beuth J (1994) Mistletoe extract standardized for the galactoside-specific lectin (ML-1) induces p-endorphin release and immunopotentiation in breast cancer patients. Anticancer Res 14 1339-1342... 

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... 

The releasing hormone CRH 40, isolated as a linear peptide-amide with 41 amino acids from ovine hypothalami by Vale et al.81) in 1981, has certain structural similarities with angiotensinogen. It stimulates the secretion of corticotropin and P-endorphin. In 1985 Morell et al.82) synthesized ovine CRH by the solid-phase method. 

Jacobowitz R, Callahan P, Janik, J (1997) Immunoneutralization of P-endorphin blocks prolactin release during suckling without affecting tuberoinfundibular dopaminergic neural activity. Life Sci 67 1301 1311. 

Selmanoff MK, Gregerson KA (1986) Suckling-induced prolactin release is suppressed by naloxone and stimulated by P-endorphin. Neuroendocrinology 42 255-259. 

Since the discovery and characterization of P-endorphin (31 amino acids) as an opioid peptide in 1976, the opinion has been widely held that this peptide has a role in the control of pain (Akil et al., 1984 Basbaum and Fields, 1984 Loh et al 1976 Rossier et al., 1977). POMC-derived P-endorphin is considered to be a key component of the endogenous antinociceptive system attenuating the stress- and inflammation-induced hyperalgesia (Rossier et al., 1977 Stein et al., 1990 Sun et al., 2003). It binds with high affinity to both MOR and DOR (Akil et al., 1984). Pain stimulation induces PAG release of 3-endorphin and the ICV administration of 3-endorphin produces analgesia (Akil et al., 1984). Similarly, both spinal and peripheral administration of 3-endorphin evokes antinociceptive effects in different pain models (Chung et al., 1994 Stein et al., 1990 Suh et al., 1994 Suh et al.,... 

P-lipotropic hormone lipotropin. lipotropin ( 5-lipotropic hormone LPH) is a linear peptide with 90 amino acid residues, p-lipotropin itself contains the sequences of y-lipotropin (a less potent lipotropic hormone), P-melanotropin (P-MSH), [Met ] enkephalin and P-endorphin. It is an anterior pituitary hormone derived from propiomelanocortin, and has endocrine functions. P-lipotropin stimulates the release of fatty acids from adipose tissue. There is a high degree of sequence homology... 

In addition to P-endorphin, P-LPH contains the amino acid sequence of another endogenous opioid, met-enkephalin. However, this peptide is not the product of P-LPH breakdown, but rather arises from a precursor molecule loiown as pro-enkephalin. Pro-enkephalin is widely distributed in neurons throughout the brain and spinal cord. Some pro-enkephalin is found in the pituitary gland, but most is localized in the catecholamine-synthesizing cells of the adrenal medulla and is co-released with epinephrine and norepinephrine. In the medulla, pro-enkephalin gives rise to met-enkephalin (Tyr-Gle-Gle-Phe-Met) and leu-enkephalin (Tyr-Gle-Gle-Phe-Leu) and to larger opioid peptides. A third family of endogenous opioid peptides is derived from prodynorphin, a prohormone stored primarily in the poste-... 

The immune system plays a major role in pain. Under pain situations, IL-1 induces a decrease inthe level of CRF, cortisol, and p-endorphin (Bessler, et al., 1996 Parsadaniatz, et al., 1997). CRF alone releases p-endorphin. IL-1 alone has the similar effect—releasing P-endorphin. n-3 Fatty acids protected the rats from opiate side effects (Frances, et al., 1996, Hargreaves et al., 1990, Jones et al., 1999). IL-1, on the other hand, increases the level of PGE2 (Hori, et al., 1998) to increase pain sensation. 

Since P-endorphin is located within the hypothalamus and the pituitary, and has a relatively longer duration of action, it tends to be viewed as a neurohormone. Enkephalins, on the other hand, are more extensively distributed, are very rapidly degraded, and are primarily located in synaptosomal areas. The additional observation that enkephalin release following depolarization of brain (and intestinal) tissues is calcium dependent makes it more realistic to categorize them as neurotransmitters or modulators of synaptic function. Binding sites (receptors) for opioids are found, particularly in synaptosomal brain fractions. The enkephalins are located in neurons whose distribution correlates well with that of the receptors. In fact, regional distribution of peptides and their receptors are closely parallel, as would be predicted for a neurotransmitter system. 

The administration of ji agonists increases the concentration of prolactin in plasma, probably by reducing the dopaminergic inhibition of its secretion. The administration of morphine or P-endorphin has little effect on the concentration of growth hormone in plasma. With chronic administration, tolerance develops to the effects of morphine on hypothalamic releasing factors. Patients maintained on methadone reflect this phenomenon in women, menstrual cycles that had been disrupted by intermittent use of heroin return to normal in men, circulating concentrations of LH and testosterone return to the normal range. 

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