Neurotransmitters neurokinin

The neuropeptides are peptides acting as neurotransmitters. Some form families such as the tachykinin family with substance P, neurokinin A and neurokinin B, which consist of 11 or 12 amino acids and possess the common carboxy-terminal sequence Phe-X-Gly-Leu-Met-CONH2. Substance P is a transmitter of primary afferent nociceptive neurones. The opioid peptide family is characterized by the C-terminal sequence Tyr-Gly-Gly-Phe-X. Its numerous members are transmitters in many brain neurones. Neuropeptide Y (NPY), with 36 amino acids, is a transmitter (with noradrenaline and ATP) of postganglionic sympathetic neurones. 

Substance P is a member of a group of polypeptides known as neurokinins or tachykinins. It is thought to be the primary neurotransmitter for the transfer of sensory information from the periphery to the spinal cord and brain. Substance P as well as neurokinin NKX receptors has been detected in vagal afferent neurons in the area postrema, nucleus tractus solitarius and dorsal motor nucleus of the vagus. Substance P has been shown to increase the firing rate of neurons in the area postrema and nucleus tractus solitarius and to produce retching when applied directly to these areas in animal studies. 

Substance P, an undecapeptide, is abundant both in the periphery and in the central nervous system. It is usually co-localized with one of the classical neurotransmitters, most commonly serotonin. Substance P is thought to have a role in the regulation of pain, asthma, psoriasis, inflammatory bowel disease and, in the CNS, emesis, migraine, schizophrenia, depression and anxiety. The substance-P-preferring receptor neurokinin-1 has been focused on most intensively in drug development, and existing... 

Numerous neurotransmitter receptors are located in the vomiting center, CTZ, and GI tract. Examples of such receptors include cholinergic and histaminic, dopaminergic, opiate, serotonin, neurokinin (NK), and benzodiazepine receptors. Theoretically, chemotherapeutic agents, their metabolites, or other emetic compounds trigger the process of emesis through stimulation of one or more of these receptors. 

A5 and C primarily project to lamina II and V of the dorsal horn, where they synapse onto local interneurons or directly onto upward-projecting neurons (figure 8.1). These primary afferents release a number of neurotransmitters to relay pain, including glutamate, aspartate, substance P, neurokinin A and B, and calcitonin gene-related peptide (table 8.1). NMDA, non-NMDA and neurokinin receptors are involved in re-... 

Substance P (SP) is a member of the family of tachykinin peptides that also includes neurokinin A and B. Their respective receptors are tachykinin NKl, tachykinin NK2 and tachykinin NK3. Substance P is best known as a pain neurotransmitter, but it also controls vomiting. In relation to emesis, its sites of localisation include the area postrema and the nucleus tractus solitarius. 

FIGURE 5—66. Substance P and its related neurokinins are present in areas of the brain such as the amygdala that are thought to be critical for regulating emotions. The neurokinins are also present in areas of the brain rich in monoamines, which suggests a potential regulatory role of monoamine neurotransmitters, which are already known to be important in numerous psychiatric disorders and in the mechanisms of action of numerous psychotropic drugs. 

Substance P and neurokinin 1 receptors. The first neurokinin was discovered in the 1930s in extracts of brain or intestine. Since it was prepared as a powder, it was called substance P. This molecule is now known to be a string of 11 amino acids (an undecapeptide) (Fig. 5—67). This is in sharp contrast to monoamine neurotransmitters, which are modifications of a single amino acid. 

Neurokinin B and neurokinin B receptors. The third important member of the neurokinin neurotransmitter family is neurokinin B (NK-B). Like NK-A, it is a ten amino acid peptide (decapeptide). Six of the ten amino acids in NK-B are the same as in NK-A, and four of the last five amino acids in the N-terminal tail of NK-B are identical to substance P (Fig. 5-67). 

FIGURE 5—72. Neurokinin A and neurokinin 2 receptors, part 2. Shown here is the formation of NK-A from the gamma PPT-A protein. The beta and gamma PPT-A proteins are the grandparents of NK-A and are cut down to size just as described for substance P, eventually forming the peptide neurotransmitter NK-A. Neurokinin A specifically binds to the NK-2 receptor. As for substance P, there is a mismatch between this neurotransmitter and its receptor anatomically, suggesting the important role of nonsynaptic volume neurotransmission for NK-A as well. However, the anatomical distribution of NK-A is different from that of substance P, and the anatomical distribution of NK-2 receptors is different from that of NK-1 receptors. 

FIGURE 5—73. Neurokinin B and neurokinin 3 receptors. The third important member of the neurokinin neurotransmitter family is NK-B, which is formed from a gene, called PPT-B, which is different from the gene from which either substance P or NK-A is derived. However, the process of converting the PPT-B protein into NK-B is analogous to that already described for substance P and NK-A. Neurokinin B prefers its own unique receptors, called NK-3 receptors. Neurokinin B and its NK-3 receptors are also mismatched and are located in different anatomical areas from substance P, NK-A, and their NK-1 and NK-2 receptors, respectively. 

Substance P and the neurokinins. The substance P and neurokinin family of peptide neurotransmitters was extensively discussed in Chapter 5 (see Figs. 5—69 through... 

Stahl, S.M. (1999) Substance P and the neurokinins, part 2 Novel peptide neurotransmitters in psychopharmacology. Journal of Clinical Psychiatry 60(2), 11—IB. 

The second section on clinical science has been increased by two chapters to accommodate the increase in the numbers of drugs and advances in knowledge about psychiatric disorders. Three new neurotransmitter systems are introduced and illustrated substance P and the neurokinin family nitric oxide and the endocannabi-noids such as anandamide (the brain s own marijuana ). Also amplified is coverage of the classical neurotransmitter systems, especially intercommunications now illustrated between serotonin and dopamine and between norepinephrine/noradrenaline and serotonin. Also included are numerous new illustrations of noradrenergic and cholinergic pathways. 

Substance P. The tachykinin receptors (NK-1, NK-2, and NK-3) and their endogenous ligands, the tachykinins, and neurokinins are important neurotransmitters (220-... 

The tachykinins are a family of small peptides (fewer than 50 residues), each of which has the same amino acid sequence, Phe-X-Gly-Leu-Met-NH2, at the amidated carboxy terminus (Fig. 7.1). Although three primary mammahan tachykinins - substance P, neurokinin A (NkA) and neurokinin B (NkB) - have been recognized, only substance P and NkA have been identified in the lungs and airways. Tachykinins are synthesized in nerve cell bodies, appropriately processed, and then transported by axoplasmic flow to the terminal ramifications of axon dendrites, where they serve their neurotransmitter functions. Both substance P and NkA are derived from transcription and translation of the preprotachykinin I (PPT-I) gene (Nawa et al., 1984 Krause etal., 1987). NkB is derived from a separate gene. 

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