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)

In the majority of autonomic ganglia, the responses to tachykinins such as substance P, neurokinin A and neurokinin B are primarily mediated by neurokinin-3 (NK-3) receptors. Neurokinin B (NK-B) and senktide are known as an endogenous tachykinin and the related peptide selective for NK-3 receptor. In this study, the generation mechanism of NK-3 receptor agonist-induced response in the hamster submandibular ganglion (SMG) cells was investigated using the current-clamp technique. The SMG cells responded to the NK-3 receptor agonists with two types of depolarizations accompanied by either a decrease or an increase in membrane input resistance. The results showed that K+ channels alone or the combination of K+ and nonselective cation channels coupled with NK-3 receptors on the SMG cells were involved in generation of the NKB- and senktide-depolarizations.
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PMID:Tachykinin-depolarizations mediated by neurokinin-3 receptors in the hamster submandibular ganglion cells. 966 46

In perfused rat skeletal muscle (hindlimb), capsaicin either stimulates (submicromolar concentrations) or inhibits (micromolar concentrations) oxygen consumption (VO2). Both VO2 effects are associated with vasoconstriction, evident as an increase in perfusion pressure (PP), under constant flow. We have proposed that these effects are mediated by two vanilloid receptor subtypes: VN1 (stimulation of VO2) and VN2 (inhibition of VO2) (; ). In the present study, the role of capsaicin-sensitive neurons and sensory neuropeptides in the VN1/VN2 receptor actions of capsaicin was investigated. The observed maximum stimulation of VO2 by capsaicin (0.4 microM; DeltaVO2, 1.35 +/- 0.14 micromol g-1 h-1) was accompanied by mild vasoconstriction (DeltaPP, 5.8 +/- 0.6 mm Hg). In contrast, 2 microM capsaicin produced strong inhibition of VO2 (DeltaVO2, -2.25 +/- 0.23 micromol g-1 h-1) with pronounced vasoconstriction (DeltaPP, 28.0 +/- 1.3 mm Hg). VO2 stimulation was significantly inhibited (P <.05) by the selective NK1 receptor antagonist CP-99994 (1 microM) and the NK2 receptor antagonist SR 48968 (1 microM) (by 42% and 51%, respectively), but PP was not altered. Infused SP and neurokinin A (NKA) stimulated VO2 (observed maximum DeltaVO2, 0.52 +/- 0.06 and 0.53 +/- 0.08 micromol g-1 h-1, respectively; EC50 values, 269 +/- 23 and 21.2 +/- 3.0 nM, respectively) and induced mild vasoconstriction (4.30 +/- 0.33 and 6. 75 +/- 1.18 mm Hg, respectively; EC50 values, 352 +/- 25.7 and 25.5 +/- 2.7 nM, respectively). Neurokinin B (NKB) also stimulated VO2 (maximum not determined) and vasoconstriction (maximum DeltaPP, 3.40 +/- 0.25 mm Hg; EC50, 34.4 +/- 5.2 nM). The rank order of potency for the tachykinins in this preparation was NKA > NKB > SP, which suggests stimulation primarily of NK2 receptors. Although infused calcitonin gene-related peptide (CGRP) did not alter hindlimb VO2 or PP, the selective CGRP antagonist CGRP(8-37) markedly potentiated the inhibition of VO2 produced by 1 microM capsaicin (84%) and the maximum capsaicin-induced vasoconstriction (57%), which indicates that endogenously released CGRP may act as a vasodilator. Hindlimbs perfused 1 day after capsaicin pretreatment showed attenuation of capsaicin-induced (0.4 microM) stimulation of VO2 (92%) (P <.05) and vasoconstriction (64%), but this returned to normal after 7 days. The inhibition of VO2 by 1 microM capsaicin was significantly (P <. 05) enhanced 7 and 14 days after pretreatment (66% and 140%, respectively), as was the maximum vasoconstriction (64% and 68%, respectively). These data suggest that capsaicin-sensitive neurons, presumably via release of SP and NKA, are involved in VN1 responses and that capsaicin pretreatment potentiates VN2 responses, either by depletion of CGRP reserves or by upregulation of putative VN2 receptors.
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PMID:Acute and chronic effects of capsaicin in perfused rat muscle: the role of tachykinins and calcitonin gene-related peptide. 980 99

The tachykinin-dependent stimulation of ion transport across frog skin was studied. Tachykinin stimulation was due to interaction with an NK1-like receptor as [Sar9-Met(O2)11]-Substance P (a very selective NK1 agonist) strongly stimulated SCC, whereas [beta-Ala8]-Neurokinin A 4-10 (a very selective NK2 agonist) did not. The rank order of tachykinin potency was: PG-KI > Uperolein > Hylambatin > Kassinin > Phyllomedusin > [Sar9-Met(O2)11]-Substance P > Ranatachykinin A > Physalaemin > Ranakinin > Substance P and Eledoisin >> Neurokinin A. Neurokinin B, Scyliorhinin I, Urechistachykinin I and Urechistachykinin II had no effect. We conclude that the minimal structural requirements for stimulating SCC in the frog skin were the presence of: a) the C-terminal sequence Phe-X-Gly-Leu-Met-NH2; b) at least one Pro residue in the N-terminal sequence.
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PMID:Actions of tachykinins on the ion transport across the frog skin. 980 59

A point mutation was made at position 289 in the transmembrane segment 7 of the human tachykinin NK2 receptor to yield a tyrosine/phenylalanine (Tyr/Phe) substitution. Chinese hamster ovary cells stably transfected with the wild-type or Tyr289Phe mutant NK2 receptor both bound neurokinin A (NKA) and the synthetic NK2 receptor-selective agonists, GR 64349 and [betaAla8]NKA(4-10), with high and even affinities. Neurokinin B (NKB) and substance P (SP) also displayed sizeable binding affinities, albeit with lower affinity as compared to NKA. In a functional assay (production of inositol-1,4,5-trisphosphate, IP3), NKA, GR 64349, and [betaAla8]INKA(4-10) stimulated IP3 accumulation via the wild-type and mutant receptors with similar potencies. On the other hand, NKB and SP exhibited a dramatic reduction in their agonist efficacies at the mutant receptor, NKB acting as a partial agonist (maximum effect = 50% of the response to NKA) and SP being totally inactive. The results obtained with phenoxybenzamine inactivation experiments indicated that a large and similar receptor reserve existed for both the wild-type and the mutant receptor. SP, which displayed sizeable binding affinity for the mutant receptor but did not stimulate IP3 accumulation, antagonized the agonist effect of NKA. The antagonist action of SP at the mutant NK2 receptor cannot be ascribed to receptor internalization. The Tyr/Phe replacement at position 289 markedly reduced the binding affinity and antagonist potency of the non-peptide ligand, SR 48968, without affecting the binding affinity and antagonist potency of the bicyclic peptide antagonist MEN 11420. The results indicate that the hydroxyl radical function of Tyr289 in transmembrane segment 7 of the human NK2 receptor is, directly or indirectly, involved in stimulus transduction when the NK2 receptor is occupied by NKB or SP, but not when using NKA or NK2 receptor-selective agonists.
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PMID:Defects of tyrosine289phenylalanine mutation on binding and functional properties of the human tachykinin NK2 receptor stably expressed in chinese hamster ovary cells. 1008 23

Neurokinin B and its cognate neurokinin-3 receptor are expressed more in the forebrain than in brain stem structures but little is known about the primary function of this peptide system in the central processing of information. In general, few studies have specifically addressed age-related changes of tachykinins, notably the changes in number and/or distribution of the neurokinin B-expressing and neurokinin-3 receptor-bearing neurons. Data on functions and changes of neurokinins in physiological aging are limited and apply mainly to the substance P/neurokinin-1 receptor system. In the present study, we analyzed neurokinin B/neurokinin-3 receptor system in young (5 months) versus middle aged (15 months) and old rats (23-25 months) and also in aging human brains. For the majority of the immunohistochemically examined regions of the rat brain, there was no statistically significant change in neuronal number and size of the neurokinin B and neurokinin-3 receptor staining. In the adult human brain, there was no age-associated change of the number or size of neurokinin-B-positive neurons. However, we found a major decline in number of neurokinin-3 receptor-expressing neurons between young/middle aged (30 years to 69 years) versus old (70 years and older) adults. Interestingly, numbers of neurokinin-3 receptor-positive microglia increased whereas the neurokinin-3 receptor-positive astrocytes remained unchanged in both aging rat and human brains. Finally, in addition to assessing the morphological and quantitative changes of the neurokinin B/neurokinin-3 receptor system in the rat and human brain, we discuss functional implications of the observed interspecies differences.
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PMID:Age and species-dependent differences in the neurokinin B system in rat and human brain. 1046 90

This study investigates the effects of intracerebroventricular injection of selective agonists and antagonists of tachykinin NK(3)receptor on performance of mice in the elevated plus-maze test. Mice were treated with either vehicle or 1, 10, 100 or 500 pmol of neurokinin B or senktide ([succinil-Asp(6), MePhe(8)]substance P(6-11), a natural and synthetic selective NK(3)receptor agonists, respectively. Other mice received similar doses of [Trp(7)beta-Ala(8)]NKA(4-10)or SR 142801 ((S)-N-(1-(3-(1-benzoyl-3-(3, 4-dichlorophenyl)-piperidin-3-yl)propyl)-4-phenyl-piperidin- 4-yl)-N-m ethylacetamide) tachykinin NK(3)receptor selective peptide and non-peptide antagonists, respectively. Senktide significantly increased the frequency of entries and the time spent in the open arms, which is compatible with an anxiolytic action. Neurokinin B treatment did not alter the plus-maze parameters in a significant way. Conversely, the NK(3)peptide antagonist [Trp(7)beta-Ala(8)]NKA(4-10), but not SR142801 non-peptide antagonist, showed a reverse effect, i.e. an anxiogenic profile of action, reducing the frequency and the time spent in the open arms. Co-injection of either senktide plus [Trp(7)beta-Ala(8)]NKA((4-10)), or senktide plus SR 142801, blocked the effects promoted by senktide, indicating that centrally-administered NK(3)receptor agonists and antagonists can modulate experimental anxiety.
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PMID:Tachykinin NK(3)receptor involvement in anxiety. 1065 89

Substance P and neurokinin B are tachykinins that derive from different precursors. Both tachykinins are known to be involved in the processing of pain-related information. Initial studies suggested an antinociceptive effect for neurokinin B, but more recent data indicate that neurokinin B facilitates nociception. Unfortunately, morphologic correlates are lacking, as little is known about the distribution of neurokinin B, especially at the ultrastructural level. Because of its potentially important role in the processing of pain-related information, we decided to investigate the synaptic interactions of neurokinin B-immunoreactive profiles in laminae I-III of the rat cervical spinal dorsal horn and their relation to substance P-immunoreactive structures. An antibody raised against a portion of the neurokinin B precursor peptide was used for the detection of neurokinin B. Neurokinin B-like immunoreactivity occurred in all superficial laminae, with the highest density in inner lamina II and the lowest in lamina III. Neurokinin B-like immunoreactive axonal boutons were mainly dome-shaped and established symmetric synaptic contacts with dendrites or cell bodies. Neurokinin B-like immunoreactivity was also detected in dendritic profiles in all superficial laminae. Some of these dendritic profiles were part of synaptic glomeruli in inner lamina II and lamina III. Double-labeling for neurokinin B and substance P showed a lack of appositions and synapses between neurokinin B and substance P-positive profiles. Furthermore, very few profiles double-labeled for the two peptides were observed. Double-labeling for gamma-aminobutyric acid (GABA) and neurokinin B showed a complete absence of neurokinin B/GABA co-localization. Furthermore, neurokinin B-positive profiles were never presynaptic to GABA-immunoreactive profiles, but frequently neurokinin B-positive dendrites were postsynaptic to GABA-immunoreactive boutons. These results suggest that neurokinin B participates in circuits separate from those involving substance P, as virtually no anatomic correlation was found between the two neuropeptides.
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PMID:Immunocytochemical localization of neurokinin B in the rat spinal dorsal horn and its association with substance P and GABA: an electron microscopic study. 1075 7

Neurokinin B (NKB) is one member of an evolutionarily conserved family of neuropeptides, the tachykinins. Preferential binding of NKB to endogenous NK(3) receptors affects a variety of biological and physiological processes, including endocrine secretions, sensory transmission, and fluid and electrolyte homeostasis. In light of its widespread biological actions, immunohistochemical detection of the c-Fos protein product was used to study the distribution of neuronal activation in the rat brain caused by intraventricular (icv) injections of the selective NK(3) receptor agonist (succinyl-[Asp(6), N-Me-Phe(8)] substance P [6-11]), senktide. Quantitative analysis revealed that treatment with isotonic saline or 200 ng senktide resulted in the differential expression of Fos-like immunoreactivity (FLI) throughout the brain. Senktide induced the highest number of FLI neurons in the lateral septum, bed nucleus of the stria terminalis, amygdala, paraventricular nucleus of the hypothalamus, median preoptic nucleus, organum vasculosum of the lamina terminalis, supraoptic nucleus, periaqueductal gray, and medial nucleus of the solitary tract compared to isotonic saline controls. Additional regions that contained elevated FLI following icv injection of senktide, relative to saline injection, included the cerebral cortex, lateral hypothalamic nucleus, suprachiasmatic nucleus, ventral tegmental area, substantia nigra, inferior colliculus, locus coeruleus, zona incerta, and arcuate nucleus. Our data indicate that activation of NK(3) receptors induces the expression of FLI within circumscribed regions of the rat brain. This pattern of neuronal activation overlaps with nuclei known to regulate homeostatic processes, such as endocrine secretion, cardiovascular function, salt intake, and nociception.
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PMID:Distribution of Fos-like immunoreactivity within the rat brain following intraventricular injection of the selective NK(3) receptor agonist senktide. 1099 47

Neurokinin B, a peptide belonging to the tachykinin family, is undetectable in peripheral tissues from nonpregnant animals. In the present study, we analysed the expression of the preprotachykinin-B (PPT-B) gene, which encodes neurokinin B, in the rat uterus. Preprotachykinin-B mRNA was expressed in the uterus and its levels varied greatly depending upon the hormonal conditions. This is consistent with a role of this tachykinin in the regulation of uterine functions.
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PMID:Expression of preprotachykinin-B, the gene that encodes neurokinin B, in the rat uterus. 1150 83

Microvascular leakage hypersensitivity is a main component of neurogenic inflammation and of tachykinin effects. The aim of this study was to examine the ability of neurokinin B and of the tachykinin NK(3) receptor agonists, [MePhe(7)]neurokinin B or senktide, to potentiate when given by aerosol the microvascular leakage induced by histamine in guinea-pig airways and to compare their effects to those of tachykinin NK(1) (substance P, [Sar(9),Met(O(2))(11)]substance P) or tachykinin NK(2) (neurokinin A, [betaAla(8)]neurokinin A (4-10)) receptor agonists. Guinea-pigs were pretreated successively for 10 min with aerolized salbutamol and phosphoramidon; 15 min later, they were exposed for 30 min to an aerosolized solution of tachykinin receptor agonists; 24 h later, the animals were anaesthetized and vascular permeability was quantified by extravasation of Evans blue dye. Neurokinin B, [MePhe(7)]neurokinin B and senktide (3 x 10(-6)-3 x 10(-5)M) induced a potentiation of the effects of histamine on the vascular permeability in the trachea and main bronchi. Compared to other tachykinin NK(1) and NK(2) receptor agonists, the order of potency was: senktide>neurokinin B=[Sar(9),Met(O(2))(11)]substance P=[betaAla(8)]neurokinin A (4-10)=[MePhe(7)]neurokinin B>neurokinin A>substance P. The potentiation by [MePhe(7)]neurokinin B of histamine-induced microvascular leakage was abolished by the tachykinin NK(1) receptor antagonist SR140333 ([(S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)piperidin-3-yl]etyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane, chloride]) or the tachykinin NK(3) receptor antagonists SR 142801 ([(R)-(N)-(1-(3-(l-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl) propyl)-4-phenylpiperidin-4-yl)-N-methylacetamide]) and SB 223412 ([(S)-(-)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carboxamide]). In conclusion, these results suggest that tachykinin NK(3) receptors might be involved in the potentiation of histamine-induced increase in microvascular permeability.
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PMID:Tachykinin NK(3) receptor agonists induced microvascular leakage hypersensitivity in the guinea-pig airways. 1175 53


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