Substance P and Neurokinin

Some propeptides lead to the production of different, in terms of receptor affinities, peptides (substance P and neurokinin A act on neurokinin 1 and 2 receptors, respectively). 

Different peptides from the same gene product (met and leu enkephalin, substance P and neurokinin A). The former two act on the same receptor, the delta opioid receptor, whereas the latter act on different receptors, the neurokinin 1 and 2 receptors. Despite this, the receptors for the neurokinins produce the same direction of effect, a slow depolarisation, even though their distribution differs. 

Seizure initiation is likely caused by an imbalance between excitatory (e.g., glutamate, calcium, sodium, substance P, and neurokinin B) neurotransmission and inhibitory (y-aminobutyric acid, adenosine, potassium, neuropeptide Y, opioid peptides, and galanin) neurotransmission. 

Mechanism of Action Aselective human substance P and neurokinin-1 (NK,) receptor antagonist that inhibits chemotherapy-induced nausea and vomiting centrally in the... 

The actions of substance P and neurokinins A and are mediated by three G protein-coupled tachykinin receptors designated NK i, NK 2, and NK 3. Substance P is the preferred ligand for the NK receptor, the predominant tachykinin receptor in the human brain. However, neurokinins A and also possess considerable affinity for this receptor. In humans, most of the central and peripheral effects of substance P are mediated by NKi receptors. All three receptor subtypes are coupled to inositol trisphosphate synthesis and calcium mobilization. 

Takeda, Y., Blount, P., Sachais, B. S., Hershey, A. D., Raddatz, R., Krause, J. E. Ligand binding kinetics of substance P and neurokinin A receptors stably expressed in Chinese hamster ovary cells and evidence for differential stimulation of inositol 1,4,5-trisphosphate and cyclic AMP second messenger responses, J. Neurochem. 1992, 59, 740-745. 

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. 

FIGURE 5-69- Substance P and neurokinin 1 receptors, part 2. Substance P can also be formed from two other proteins, called beta-PPT-A, shown here, and gamma PPT-A, shown in Figure 5 — 70. These proteins come from different mRNA splice variants but the same precursor PPT-A gene. 

FIGURE 5—70. Substance P and neurokinin 1 receptors, part 3. Shown here is how substance P is formed from gamma PPT-A. Thus, substance P can be formed from three proteins derived from the PPT-A gene, namely, alpha, beta, and gamma PPT-A (see also Figs. 5-68 and 5-69). When substance P is released from neurons, it prefers to interact selectively with the neurokinin 1 subtype of neurokinin receptor (Figs. 5-68 to 5-70). However, there is a mismatch in the brain between the locations of substance P and the NK-1 receptors, suggesting that substance P acts preferentially by volume neurotransmission at sites remote from its axon terminals rather than by classical synaptic neurotransmission. 

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... 

The stimulation of C fibers by capsaicin causes a subset of sensory airway neurons to release several neuropeptides, which include tachykinin, substance P and neurokinin A. In addition to capsaicin, other endogenous mediators including histamine, prostaglandins and bradykinins can also result in their release. These neuropeptides are responsible for neurogenic inflammation, which is characterized by vasodilation, mucus secretion, plasma protein extravasation, increased expression of the adhesion molecules and bronchoconstriction. 

Joos, G., Pauwels, R. and Van der Straeten, M. (1987). EflFect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects. Thorax 42, 779-783. 

Krause, J.E., Chirgwin, J.M., Carter, M.S. etal. (1987). Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. Proc. Natl. Acad. Sci. USA 84, 881-885. 

Warden MK, Young WS. 1988. Distribution of cells containing mRNAs encoding substance P and neurokinin B in the rat central nervous system. J Comp Neurol 272 90-113. 

In addition to stimulating afferent nerve fibre endings in mucosal surfaces and producing a typical PCSI effect, OC also induces the release of tachykinins or neuropeptides like substance P and neurokinin A. This induces neurogenic inflammation of the airway blood vessels, epithelial cells, glands and smooth muscle, leading to vasodilation, increased vascular permeability, neutrophil chemotaxis, mucus secretion and bronchospasm (Smith and Stopford, 1999). 

Limited and/or weak staining is seen at select sites and in select species for a variety of other peptide antisera (e.g., peptide histidine-isoleucine, calcitonin gene-related peptide, the tachykinin family members substance P and neurokinin A, etc. (22, 55, 91, 99)). These various immunoreactivities, though not necessarily prominent in extent or amount, nevertheless suggest the presence of a wide diversity of potentially bioactive peptides in the nervous system of parasitic flatworms. This neurochemical complexity is illustrated in cestodes where 20 different peptide immunoreactivities outnumber the seven putative classical (small molecule) transmitters reported to date for this group in the trematodes there are approximately 24 different peptide immunoreactivities in a wide range of species. These numbers will no doubt continue to increase. 

Most often more than one neurotransmitter is released at the same time. Aspartate and glutamate are excitatory amino-acids (EAAs) involved in pain transmission [4,5]. Glutamate is the main excitatory CNS nem-otransmitter and mediates rapid, short-duration depolarization of second-order neurons. Peptides such as substance P and neurokinin are responsible for delayed long-lasting depolarization. EAAs act on various receptors, which principally include alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic... 

Prabhakar NR, Landis SC, Kumar GK, MuUikin-Kilpatrick D, Chemiack NS, Leeman S. Substance P and neurokinin A in tbe cat carotid body localization, exogenous effects and changes in content in response to arterial PO2. Brain Res 1989 481 205-214. 

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