Endorphins, actions

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. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

Research into the properties of opiates has provided more insights into the processes that make up psychopharmacological actions than any other class of drug this is because opiates bind to receptor sites that are affected by endorphins - the brain s indigenous opiates. These endorphins are implicated in pain thresholds, natural highs and our capacity for addiction to opiates. 

Opioid peptide A neuropeptide (e.g., p-endorphin), whose actions are mimicked by opiate drugs. 

Weisner JB, Koeng JI, Krulich L, Moss RL (1984) Site of action for -endorphin-induced changes in plasma luteinizing hormone and prolactin in the ovariectomized rat. Life Sci 34 1463-1473... 

Electroencephalographic and cardiovascular studies of (3) have been performed [41]. There is also a detailed report on the action of (3) on the central nervous system [42] and on the effect of (3) on -endorphin release in rats [43], It has been shown that (3) does not produce physical dependence upon chronic administration to animals [44],... 

Spinella M, Znamensky V, Moroz M, Ragnauth A, Bodnar RJ. (1999). Actions of NMDA and cholinergic receptor antagonists in the rostral ventromedial medulla upon beta-endorphin analgesia elicited from the ventrolateral periaqueductal gray. Brain Res. 829(1-2) 151-59. 

Glucagon is a second pancreatic hormone that, like insulin, influences carbohydrate metabolism. However, most of its actions oppose those of insulin. The enkephalins and endorphins are the body s natural painkillers they are thought to be responsible for runner s high. These, among many others, are proteins or are closely related to them. 

Only one antagonist is known, naloxone, which is used clinically to treat opiate overdoses and, experimentally, to investigate whether physiological or biochemical actions are opiate-mediated. One example of its use is to support the hypothesis that P-endorphin is responsible for the analgesic effects of acupuncture. Not only does low frequency electroacupuncture increase p-endorphin levels in cerebrospinal fluid but naloxone nullifies the analgesic effect of this treatment. 

Substances with a neuromodulatory effect on brain neurotransmitters by direct actions of specific receptors that modify the actions of the transmitters listed include prostaglandins, adenosine, enkephalins, substance P, cholecystokinin, endorphins, endogenous benzodiazepine receptor ligands, and possibly histamine. CNS, central nervous system. NMDA, N-methyl-D-aspartate. Strych, strychnine. 

Yu BC, Chang CK, Su CF, Cheng JT. (2008) Mediation of 3-endorphin in andrographolide induced plasma glucose lowering action in type 1 diabetes like animals. Naunyn-Schmiedeberg s Arch Pharmacol 377 529-540. 

A clue to possible treatments for pain was discovered in the 1970s when scientists found specialized receptor cells in neurons called opiate receptors. These receptors appeared to he well suited for accepting natural painkillers that occur in the body, such as the enkephalins and endorphins. Enkephalins and endorphins are naturally occurring painkillers similar in their action to opium, morphine, and codeine. 

Endogenous oligopeptides that bind with parts of opioid receptors and act analogous to opioids were observed in the brain and other tissues. The first of these to be isolated and decoded were met- and leu-enkephaUn. j3-Endorphin, a peptide with quite a large molecular mass and with analogous action, was found produced in pituitary gland. 

There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of biogenic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Amino acid neurotransmitters are glutamic and aspartic acids that excite postsynaptic membrane receptors of several neurons as well as y-aminobutyric acid (GABA) and glycine, which are inhibitory neurotransmitters. Endorphins, enkephalins, and substance P are considered peptidergic transmitters. There are many compounds that imitate the action of these neurotransmitters. 

The chemical transmitters may be small molecules— notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively. Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the endogenous opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland). 

Opium is the milky exudate obtained by incising the unripe seed capsule of the poppy plant Papaver somniferum and morphine is the most important alkaloid of opium. Morphine produces analgesia through action in the brain and spinal cord, that contain peptides possessing opioid like pharmacological action. These endogenous substances are known as endogenous opioid peptides (earlier known as endorphin now known as P-endorphin). 

Calcium antagonists (e.g., verapamil, nimodipine) can also block dopamine, 5-HT, and endorphin activity, alter sodium activity via a sodium-calcium counter-exchange, and act as anticonvulsants. Any or all of these actions could be involved in their putative antimanic effects ( 35). 

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