Endorphins neurotransmitters

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. 

The POMC family consists of peptides that act as hormones (ACTH, LPH, MSH) and others that may serve as neurotransmitters or neuromodulators (endorphins) (see Figure 42-15). POMC is synthesized as a precursor molecule of 285 amino acids and is processed differ-endy in various regions of the pituitary. 

If opiates are such addictive and potentially lethal compounds, why does the body respond to them As with the cannabinoids (Chapter 7), it has been discovered that the body and brain possess numerous opiate-specific receptor sites. As many as nine receptor subtypes have been identified, with three of them being the most important p (mu), k (kappa) and 8 (delta). The finding that the distribution of opiate receptors did not parallel the distribution of any known neurotransmitter prompted the search for and identification of a number of endogenous compounds specific to these receptors. These enkephalins and endorphins are manufactured within the brain and other body systems (especially the gut and intestines) and form the body s natural response to pain. They appear to be produced in bulk chains of amino acids called polypeptides , with each active neurotransmitter being composed of around five amino acid molecules. These active neurotransmitters are subsequently cleaved from the larger polypeptides at times of demand for example, it has been demonstrated that the plasma levels of these active compounds rise during childbirth, traumatic incidents and vigorous physical exercise. 

The body modulates pain through several processes. The endogenous opiate system consists of neurotransmitters (e.g., enkephalins, dynorphins, and /1-endorphins) and receptors (e.g., fl, S, k) that are found throughout the CNS. Endogenous opioids bind to opioid receptors and modulate the transmission of pain impulses. 

Neurotransmitten Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic deft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic add, substance P, enkephalins, endorphins, and serotonin. [EU]... 

Figure 1.2 Serotonin is one of the brain s neurotransmitters. This image depicts serotonin transmission between neurons and the drug Ecstasy s effects on that transmission. Serotonin is normally removed from the synapse shortly after being released. Ecstasy blocks this mechanism, increasing the amount of serotonin in the synapse. This causes the postsynaptic neuron to be overstimulated by serotonin. Serotonin is one of many neurotransmitters that nerve cells can secrete. Other common neurotransmitters include dopamine, glutamate, gamma aminobutyric acid (GABA), noradrenaline, and endorphins.

Opiate drugs encompass morphine and its many synthetic derivatives including heroin. Opiates act by mimicking endogenously occurring morphine-like neurotransmitter peptides termed the enkephalins or endorphins. 

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. 

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). 

There are three principal classes of opiate receptors, designated x, K, and 5, and there exist a number of drugs that are specific for each of these receptor types. However, most of the clinically used opiates are quite selective for the preceptor the endogenous opiates enkephalin, endorphin and dynorphin are selective for the p and 5, 5 and k receptors respectively. When activated by opioids these receptors produce biochemical signals that block neurotransmitter release from nerve terminals, a process that underlies their blockade of pain signaling pathways as well as other effects, such as constipation, diuresis, euphoria, and feeding. 

Endorphins, dynorphins, and enkephalins are natural peptide neurotransmitters that activate the opioid... 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

The effects of morphine eventually led many scientists to predict that the brain possesses its own endogenous opiate-like neurotransmitters and its own complement of endogenous opiate receptors in the brain. In the mid-i97o s research confirmed that the brain and body do indeed contain some endogenous morphine-like peptides and christenedthem endorphins. These peptides control our experience of pain by stopping the flow of pain signals into our brains, and this action is enhanced... 

ENDOGENOUS OPIOIDS Naturally occurring opioids in the body includes three classes of neurotransmitters—the endorphins, enkephalins, and dynorphins. 

J(delta) Supraspinal and spinal analgesia modulation of hormone and neurotransmitter release Enkephalins > > endorphins and dynorphins... 

Although similar in primary structure to proteins, endorphins are smaller, ranging from five to forty or more amino acids in length. Endorphins are not considered to be neurotransmitter molecules, but are instead classified as neuromodulatory, that is, they modify the action of neurotransmitters through a number of effects associated with pain or pleasure. 

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