Neurotransmitters acid enkephalins

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. 

Figure 1.1 The chemical structures of the main neurotransmitters. The relatively simple structure of acetylcholine, the monoamines and the amino acids contrasts with that of the peptides, the simplest of which are the enkephalins which consists of five amino acids substance P has eleven...

Lamina II is also known as the substantia gelatinosa (SG) and can be divided into two layers, the outer layer (IIo) and the inner layer (Ili). This layer is densely packed with small neurons and lacks myelinated axons. Neurons with cell bodies in Hi receive inputs from low-threshold mechanoreceptive primary afferents, while those in IIo respond to inputs from high-threshold and thermoreceptive afferents. The intrinsic cells which comprise the SG are predominantly stalk and islet cells. Stalk cells are found located in lamina IIo, particularly on the border of lamina I, and most of their axons have ramifications in lamina I although some also project to deeper layers. These cells are thought to predominantly relay excitatory transmission. Islet cells, on the other hand, are located in Hi and have been demonstrated to contain the inhibitory neurotransmitters, y-aminobutyric acid (GABA), glycine and enkephalins in their dendrites. Hence these cells have been proposed to be inhibitory interneurons. 

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. 

Most studies to date have focused on monoamine systems therefore, it would be of interest to examine the effects of hallucinogenic drugs on the neurochemistry, specific receptor binding, and electrophysiology of other putative neurotransmitter and peptide systems, such as y-aminobutyric acid, glycine, acetylcholine, enkephalin, and substance P. 

There is now evidence that the mammalian central nervous system contains several dozen neurotransmitters such as acetylcholine, noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), together with many more co-transmitters, which are mainly small peptides such as met-enkephalin and neuromodulators such as the prostaglandins. It is well established that any one nerve cell may be influenced by more than one of these transmitters at any time. If, for example, the inhibitory amino acids (GABA or glycine) activate a cell membrane then the activity of the membrane will be depressed, whereas if the excitatory amino acid glutamate activates the nerve membrane, activity will be increased. The final response of the nerve cell that receives all this information will thus depend on the balance between the various stimuli that impinge upon it. 

At least 15 endogenous peptides have now been discovered, varying in length from 5 to 33 amino acids (the enkephalins and the endorphins). These compounds are thought to be neurotransmitters or neurohormones in the brain and operate as the body s natural painkillers as well as having a number of other roles. They are derived from three inactive precursor proteins—proenkephalin, prodynorphin, or proopiomelanocortin (Fig. 12.38). 

The endogenous opiates include -endorphin, the enkephalins (met-enkephalin and leu-enkephalin), the dynorphins, and the neoendorphins. All are peptides, varying in size from 5 to 31 amino acid residues. All have in common an amino terminus consisting of either of two pentapeptide sequences Try-Gly-Gly-Phe-Met (the met-enkephalin sequence) or Tyr-Gly-Gly-Phe-Leu (the leu-enkephalin sequence). The fundamental endogenous opioid peptides are the pentapeptides, met-enkephalin and leu-enkephalin which function as neurotransmitters in the CNS. 

Spiny projection neurons all contain glutamic acid decarboxylase (GAD) the synthetic enzyme for the neurotransmitter GABA (Kita and Kitai 1988). In addition, most of those neurons projecting to the globus pallidus alone contain the neuropeptide enkephalin, whereas most of those which project to the substantia nigra contain the neuropeptides substance P and dynorphin (Beckstead and Kersey 1985 Gerfen and Young 1988 Haber and Watson 1983). Spiny projection neurons contain different complements of neurotransmitter receptors, and other proteins that serve to characterize particular subpopulations of striatal output neurons. These will be discussed in further detail below. 

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 cleft 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 acid, substance P, enkephalins, endorphins, and serotonin. [EU]... 

SP, a number of neurotransmitters that are still putative include other neuronal peptides (enkephalins, endorphins) and peptides that act as hormones elsewhere (e.g., angiotensin I and II, prolactin, somatostatin) as well as other amino acids. The number easily exceeds 50 substances, with no end in sight. Other small molecules that may be called the also suggested category include such candidates as ATP, c-AMP, GTP, c-GMP, estrogen, corticosterone, and even several prostaglandins. They will not be considered in this brief overview. 

There are many small oligopeptides that serve as neurotransmitters and hormones. The enkephalins, endorphins, etc. have already ben mentioned in the section on opiate receptors. Two amino acids that serve in this way are glycine, an inhibitory transmitter, and glutamic acid, an excitatory transmitter. gamma-Aminobutyric acid (GABA) is less well established, but probably an inhibitory transmitter. Peptide hormones like vasopressin and somatostatin are made in the pituitary gland or hypothalamus and influence processes elsewhere in the body. 

It is interesting to consider the enkephalins as Nature s simplification, for certain purposes, of the endorphins (Section 12.8). For his part, Man has successfully shortened some of Nature s bioactive polypeptides, as in the deletion of the first three of its amino acids from the undecapeptide neurotransmitter. Substance P. Again the synthetic pentapeptide, pentagastrin, is used to... 

Several amino-acids are important neurotransmitters in the c.n.s. Glutamic and aspartic acids seem to be excitatory transmitters in the entire brain. y-Aminobutyric acid (GABA) and glycine are important inhibitory transmitters, the former in supraspinal interneurons and the latter at spinal interneurons (Curtis and Johnston, 1970). Of the polypeptide neurotransmitters, the most studied have been the endorphins and enkephalins (see Section 12.8), Substance P (an undecapeptide that helps transmit the sense of pain (von Euler and Pernow, 1977, somatostatin, and gastrin, and cholecystokinin whose action in the gut has been well researched. For more on GABA, see Section 12.7. 

Davidson, N. Neurotransmitter Amino Acids. Academic Press, London 1976 Miller, R. J., Cuatrecasas, P. The enkephalins, peptides with morphine-like activity. Natur-wissenschaften 65, 507-514 (1978)... 

The reported neurochemical effects of lead are, as has been seen, enormous. They can be broadly summarized by neurotransmitter system cholinergic impairment at relatively high levels (usually in the presence of non-specific effects), dopaminergic effects at low levels, and impairment at higher levels (in the presence of obvious non-specific effects), GABAergic effects at levels where a complication from the interaction with D-amino laevulinic acid also occurs. There is also a mixed bag of effects on enkephalin, adenyl cyclase, 5-hydroxytrypamine and other putative aminergic neurotransmitters. 

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