Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of neurokinin B was investigated in the basal forebrain of the rat by immunocytochemistry with an antibody directed against neurokinin B, and with a second antiserum directed to a peptide sequence contained within its precursor, and by means of in situ hybridization. The staining pattern was compared in closely adjacent sections to that of substance P- and enkephalin-like immunoreactivities. Cholecystokinin immunoreactivity was used to delineate the apparent dorsolateral border of the ventral pallidum with the nucleus accumbens. Remarkable similarities are found in the distribution of these peptides in the basal forebrain, especially in its ventral part. The coarse band-like terminal staining pattern (woolly fibers) that has been shown by others for substance P- and enkephalin-like immunoreactivity, is also observed for neurokinin B-like immunoreactivity, mainly in the ventral pallidum. Medium-sized cells are found arranged in clusters or singularly within the caudate-putamen even without colchicine. A band of strong neurokinin B immunoreactivity extends just underneath the dorsal pallidum to the amygdala. In comparison to enkephalin the most distinct observation is that neurokinin B immunoreactivity is not present in the dorsal pallidum (global pallidus). Neurokinin B immunoreactivity was not found in the pars reticulata of the substantia nigra which is strongly immunopositive for substance P. The number of cells detected by in situ hybridization was higher compared to the immunopositive perikarya throughout the basal ganglia. The staining pattern observed reflects a partial overlap with the substance P and enkephalin system although a differential distribution for each of these peptides was observed for cell bodies and axons terminals.
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PMID:Comparative distribution of neurokinin B-, substance P- and enkephalin-like immunoreactivities and neurokinin B messenger RNA in the basal forebrain of the rat: evidence for neurochemical compartmentation. 128 22

The neuropeptide substance P is found in perivascular and free unmyelinated nerve fibres in human synovial tissue. Quantitative receptor autoradiography was used to show specific, high affinity (Kd = 0.75 (0.21), nmol/l (mean (standard error of the mean)), low capacity (Bmax = 27.8 (7.9) amol/mm2) binding sites for substance P Bolton Hunter-labelled with iodine-125 localised to vascular endothelial cells in human synovial tissue. The binding could be saturated, was reversible, and was dependent on the magnesium concentration. Unlabelled substance P and neurokinin A competitively inhibited specific binding with 50% inhibition at concentrations of 1.25 (0.21) and 175 (29) nmol/l respectively. Neurokinin B (mumol/l) and calcitonin gene related peptide (1 mumol/l) did not inhibit binding. These binding sites show characteristics of the neurokinin 1 tachykinin receptor subtype. This provides further evidence that substance P may play a part in the vascular control of human synovium and may influence inflammatory processes in joints.
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PMID:Localisation and characterisation of substance P binding to human synovial tissue in rheumatoid arthritis. 137 27

Functional cDNA clones encoding the human neurokinin-3 receptor were isolated from human brain mRNA. The cloned human neurokinin-3 receptor was expressed in COS cells and Xenopus oocytes, where peptide binding affinity and intracellular effector activation were determined. Neurokinin B is the most potent agonist, followed by eledoisin, substance K and substance P. The binding affinities of these peptides at the human neurokinin-3 receptor differ quantitatively from the rat receptor, implying a functional consequence of the sequence divergence between the two species. Heterologous expression in oocytes revealed that, unlike the neurokinin-1 receptor, the efficacy of ion channel activation mediated by the neurokinin-3 receptor does not approximate the binding affinity. The heterologous expression of the human neurokinin-3 receptor will facilitate further investigation into its biochemical functions.
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PMID:cDNA sequence and heterologous expression of the human neurokinin-3 receptor. 137 46

Neurokinin B (NKB) belongs to the family of neuropeptides named tachykinins. Members of this family such as substance P or neurokinin A have been proposed to function as neurotransmitters or neuromodulators. Searching for possible sites of action of NKB in the central nervous system, we have now investigated its distribution within the rat brain by immunohistochemical techniques and in situ hybridization. For immunohistology two different antisera directed against amino acid sequences within preprotachykinin B were used. One antiserum had been raised against a synthetic derivative of NKB; the other one was directed towards the amino acids 50-79 of preprotachykinin B, which are referred to as peptide 2. Essentially the same distribution of immunoreactive perikarya was obtained with both antisera and it closely corresponded to the cellular localization of preprotachykinin B mRNA. Neurons containing NKB immunoreactivity and mRNA were present in many areas including cerebral cortex, hippocampal formation, amygdaloid complex, bed nucleus of the stria terminalis, ventral pallidum, habenula, medial preoptic area, arcuate nucleus, and lateral mammillary bodies. Dense immunoreactive fibers were observed in various parts of the brain and were most prominent in the olfactory bulb and tubercle, the lateral olfactory tract, medial hypothalamus, around blood vessels of the median eminence and interpeduncular nucleus, amygdaloid nuclei, stria terminalis, subbrachial nucleus, and medial geniculate nucleus. Fibers of less intense staining were seen among other brain areas in the substantia nigra, the reticular formation, and the area of the nucleus of the solitary tract. Surgical lesion of the fasciculus retroflexus revealed that the dense fiber network observed in the interpeduncular nucleus originates from the ventral and dorsal parts of the medial habenula. Our data suggest a widespread and distinct distribution of neurons expressing NKB within the central nervous system, suggesting possible neuromodulatory roles of this neuropeptide for various brain functions.
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PMID:Distribution of neurons expressing neurokinin B in the rat brain: immunohistochemistry and in situ hybridization. 137 42

In the present study, highly specific radioimmunoassays were developed and used to measure neurokinin B, neurokinin A and substance P in the rat spinal cord and various peripheral tissues. The results are as follows. (1) Neurokinin B and neurokinin A were distributed all along the rostrocaudal axis of the spinal cord, as is substance P, and were more concentrated in the dorsal than in the ventral region. (2) Substance P was more abundant in the central and peripheral nervous tissues than neurokinin A, while in certain peripheral organs, neurokinin A was more abundant than substance P. In the spinal cord, neurokinin B concentrations were lower than those of the other two tachykinins. (3) In contrast to neurokinin A and substance P, neurokinin B was not detected in any of the peripheral tissues examined. (4) Capsaicin treatment reduced by half neurokinin A and substance P concentrations in the dorsal region of the spinal cord, the dorsal root ganglia and the sciatic nerve, but was without effect on neurokinin B concentrations in the spinal cord. Neurokinin A, like substance P, may therefore have an important function in the transmission of sensory information, particularly in nociceptive transmission from the periphery to the spinal cord and in peripheral neurogenic inflammation. In contrast, since neurokinin B was not found in the sensory neurons, it is not likely to have these functions, but may perhaps control them.
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PMID:Distribution of neurokinin B in rat spinal cord and peripheral tissues: comparison with neurokinin A and substance P and effects of neonatal capsaicin treatment. 137 79

Substance P and selective neurokinin receptor agonists have been tested for their ability to induce shape change in rabbit platelets. Substance P and the NK1 receptor agonist Ac [Arg6,Sar9,Met(O2)11]-substance P (6-11) induced shape change (EC50 = 3 and 6 nM, respectively), whereas the selective NK2 agonist [Nle10]-Neurokinin A (4-10) and the selective NK3 agonist [MePhe7]-Neurokinin B did not show any effect. Moreover, the specific NK1 receptor antagonist CP-96,345 selectively and dose-dependently counteracted the effect of substance P or of the NK1 receptor agonist (IC50 = 2 and 0.8 nM, respectively), whereas the selective NK2 receptor antagonist, SR 48968, had no effect. Unlike for serotonin or low doses of ADP, epinephrine did not allow substance P or the NK1 receptor agonist to become a proaggregating substance. These data therefore show that the NK1 receptor is solely involved in the neurokinin-induced shape change of rabbit platelets.
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PMID:The NK1 receptor is involved in the neurokinin-induced shape change of rabbit platelets. 138 16

In membranes of dogfish brain and stomach, two binding sites for tachykinins were identified. One site specifically bound [125I]-Bolton-Hunter substance P (BH-SP) and the rank potency of tachykinins to compete for BH-SP binding revealed similarities with the rank potency of an NK1 receptor. The pharmacology of the other site, which specifically bound [125I]-Bolton-Hunter scyliorhinin II (BH-Scy II), did not resemble any of the mammalian tachykinin receptors. The rank potency to inhibit BH-Scy II binding to this second site was: scyliorhinin II approximately scyliorhinin I greater than eledoisin approximately substance P approximately neurokinin A greater than phyllomedusin approximately physalaemin greater than [Sar9Met(O2)11]substance P. Neurokinin B and senktide did not displace BH-Scy II binding. In addition, nucleotide analogues inhibited BH-SP binding but not BH-Scy II binding. Our binding data suggest the existence of a mammalian-like NK1 receptor and of a nonmammalian tachykinin receptor in the dogfish.
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PMID:Binding sites for tachykinin peptides in the brain and stomach of the dogfish, Scyliorhinus canicula. 166 86

Lower esophageal sphincter (LES) effects produced by the mammalian tachykinins were evaluated in anesthetized dogs. The distribution and content of substance P (SP) and neurokinin A (NKA) in the region of the canine gastroesophageal junction was also studied. SP and NKA stimulated a linear dose-dependent contraction of the LES after intra-arterial administration. Neurokinin B (NKB) failed to stimulate an increase in LES pressure (LESP). SP was characterized by an immediate but short-lived contraction followed by a period of relaxation. NKA stimulated a potent LES contraction that was slow in onset but long-lasting. On an equimolar basis, both SP and NKA were approximately 100 times more potent LES stimulants than bethanechol or phenylephrine. Pretreatment with atropine (muscarinic blockade) or tetrodotoxin (neural blockade) inhibited the effect produced by SP. NKA appeared to stimulate LES contraction independent of neural or cholinergic mechanisms. Radioimmunoassay revealed a regional variation in tachykinin content in the gastroesophageal junction. Ganglia, cell bodies, nerve fascicles, and neurites stained specifically for both SP and NKA. The variable effects, potencies, and mechanisms of action observed in this study suggest the presence of specific tachykinin receptor subtypes in the gastroesophageal junction. Both SP and NKA were found to have a broad neural distribution in this region. These findings suggest that the tachykinins may play an important role in neuroregulation of LES smooth muscle.
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PMID:Tachykinins in the canine gastroesophageal junction. 170 40

Neurokinin A and neurokinin B may play a role in control of the peripheral circulation in either physiological or pathophysiological conditions. We have infused these peptides intra-arterially at three infusion rates each to assess their actions on vascular pressures, blood flows and total and segmental resistances in skin and skeletal muscle in the canine forelimb. Neurokinin A infusions (.01, .1, and 1 micrograms/min) decreased total forelimb resistance; transiently, 26% and 57%, respectively. The decrease in resistance was equally distributed between the skin and skeletal muscle circulations and was manifest in both large artery and small vessel resistances. Systemic and forelimb arterial pressures were decreased in a dose-dependent manner. Neurokinin B infusions (.5, 1 and 5 micrograms/min) decreased total forelimb resistance 29%, 31%, and 52%, respectively. The decrease in resistance was equally distributed between the skin and skeletal muscle circulations and was the result of decreases in both large artery and small vessel resistances. Systemic and forelimb arterial pressures were decreased in a dose-dependent manner. The potent effect of neurokinins on vascular resistance and their concentration in perivascular nerves innervating the resistance vessels of the circulation suggests a potential role for these neuropeptides in circulatory control.
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PMID:Neurokinin A and B: potent vasodilators in the canine forelimb. 170 97

Three types of binding sites for the mammalian tachykinins, ie Substance P (SP) Neurokinin A (NKA) and Neurokinin B (NKB), have been found in both the central and peripheral nervous systems. Substance P binds to the NK-1 subclass of binding site while NKA and NKB are less selective endogenous ligands, which preferentially interact with the NK-2 and NK-3 subclasses of binding sites, respectively. Complementary strategies, including 3-dimensional structure analysis by NMR spectroscopy and structure-activity relationship led to the design of selective agonists of these binding sites. [Pro9] SP, [Pro10] SP and the cyclic analogues [Cys3,6, Tyr8, Pro9] SP and [Cys3,6, Tyr8, Pro10] SP are selective NK-1 agonists. [Lys5] NKA(4-10) is a water soluble NK-2 potent agonist. Finally, [Pro7] NKB, which completely discriminates NK-2 and NK-3 binding sites, is a water-soluble NK-3 selective agonist.
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PMID:Selective agonists of tachykinin binding sites. 216 64


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