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)

1. We evaluated the effects of neurokinins, tachykinin analogues, or capsaicin on passive membrane properties of guinea-pig bronchial parasympathetic neurones using intracellular recording techniques. 2. Substance P (SP) and the tachykinin analogue, acetyl-[Arg6,Sar9,Met(O2)11]-SP(6-11) (ASMSP), at concentrations selective for the neurokinin (NK)-1 receptor subtype, depolarized the resting potential (3 and 5 mV, respectively) with no change in input resistance. Neurokinin A and beta Ala8NKA(4-10), at concentrations selective for the NK-2 receptor subtype (0.1 microM), were without effect. 3. Neurokinin B (NKB) and [Asp5,6,methyl-Phe8]SP(5-11) (senktide analogue), at concentrations selective for NK-3 receptor subtype, elicited maximum depolarizations of 16 +/- 2 mV for both agonists. The peak of the depolarization was associated with an decrease in membrane resistance (35 +/- 4 and 50 +/- 7%, respectively). 4. Capsaicin (1 microM) elicited a 3-24 mV depolarization of the resting potential of thirteen of eighteen bronchial ganglion neurones and decreased the input resistance of seven of thirteen of these neurones. The effects of capsaicin were reduced by desensitization with senktide analogue at a concentration selective for the NK-3 receptor subtype, whereas a non-peptide NK-1 receptor antagonist had no effect. 5. Using voltage clamp analysis, capsaicin and senktide analogue evoked an inward current and an increase in membrane conductance at the resting membrane potential. The reversal potential for senktide analogue was estimated to be + 4 mV. 6. These data support the hypothesis that neurokinin-containing nerve terminals are localized within guinea-pig bronchial parasympathetic ganglia and, when released, the predominant effect of the neurokinins is by activation of NK-3 receptors.
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PMID:Electrophysiological effects of tachykinins and capsaicin on guinea-pig bronchial parasympathetic ganglion neurones. 750 8

Capsaicin at low concentrations increases the short circuit current (SCC) across frog skin. Simultaneous measurements of both transepithelial fluxes of 22Na or 36Cl demonstrate that the SCC increase is due to stimulation of sodium active absorption. Capsaicin acts through the liberation of several peptides; thus these peptides were tested on the SCC across frog skin. Those more active are, in order of potency: Cyclic Calcitonin Gene Related Peptide (CGRP), Kassinin and Eledoisin, Substance P (SP) and Neurokinin A. Neurokinin B and Vasoactive Intestinal Peptide (VIP) have no effect. Also the actions of SP and CGRP are due mainly to stimulation of Na+ active absorption. A strict parallelism regarding the sensitivity to inhibitors (Naproxen, SQ22536 and CP96345) between SP, CGRP and Capsaicin strengthens the hypothesis that SP and CGRP are liberated by Capsaicin in this tissue.
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PMID:Action of capsaicin and related peptides on the ionic transport across the skin of Rana esculenta. 751 33

Ninety-five percent of the neurons in the corpus striatum of the rat are medium spiny projection neurons, which contain tachykinins such as substance P, neurokinin A, and neurokinin B and the opiate peptides, enkephalin and dynorphin. The remaining 5% consist of interneurons, of which a small but significant proportion are cholinergic. The influence of these cholinergic interneurons on the neuropeptidergic projection systems in the striatum is poorly understood at this time. The present study explores the relationship between cholinergic receptor activation or muscarinic blockade on striatal neuropeptide gene expression. Adult male Sprague-Dawley rats were treated chronically either with a cholinergic agonist (physostigmine: 0.5 mg/kg/3 x day), a muscarinic antagonist (scopolamine HCl: 0.4 mg/kg/3 x day), or vehicle (PBS: 0.1 ml/100 g) administered for 6 days (s.c.). In situ hybridization was performed with probes directed against mRNAs for beta-preprotachykinin (a transcript containing substance P, neurokinin A, and other tachykinins), neurokinin B and preproenkephalin. Physostigmine administration resulted in a 12% decrease in the dorsolateral caudate-putamen and a 27% increase in the core of the nucleus accumbens in substance P/neurokinin A mRNA; and a 29% increase in the caudate-putamen and an 11% increase in the core of the nucleus accumbens in preproenkephalin mRNA levels. Scopolamine treatment resulted in a 28% and 48% decrease, respectively, in the caudate-putamen and in the shell of the nucleus accumbens in substance P/neurokinin A mRNA levels. Neurokinin B mRNA levels were increased by 50% in the shell of the accumbens after scopolamine. Preproenkephalin mRNA levels increased by 24% in the caudate-putamen and decreased by 20% in the core of the nucleus accumbens. From these results we tentatively conclude that cholinoceptive neuropeptidergic neurons are segregated along dorsoventral and mediolateral axes in the striatum, thus giving rise to non-homogenous responses upon cholinergic receptor activation or muscarinic blockade.
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PMID:Cholinergic regulation of tachykinin- and enkephalin-gene expression in the rat striatum. 763 70

In this study, we investigated the cardiovascular effects of four tachykinins in the anaesthetized toad, Bufo marinus. The potencies were compared of the amphibian peptides ranakinin and physalaemin and the mammalian peptide substance P, all of which interact preferentially with tachykinin NK-1 receptors. Neurokinin B, which is found in both mammals and amphibians, was also tested. All tachykinins produced dose-dependent decreases in arterial blood pressure. Ranakinin caused significantly greater falls in blood pressure than substance P, and the response was of longer duration. Both ranakinin and physalaemin were significantly more potent at decreasing blood pressure than neurokinin B. The NK-3 receptor selective agonist, senktide, caused no change in blood pressure. No tachykinin, at doses up to 10 nmole/kg, produced effects on baseline heart rate or affected the ability of the vagus nerves to slow the heart. A non-peptide NK-1 receptor antagonist, CP96,345 (in the dose range 10(-10)-5 x 10(-7) moles/kg) had no effect on the depressor action of ranakinin or substance P. It is concluded that amphibian tachykinins cause depressor effects via an NK-1-like receptor which differs substantially from its mammalian counterpart.
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PMID:Cardiovascular effects of amphibian and mammalian tachykinins in the toad, Bufo marinus. 768 77

We have examined the effect of various natural and synthetic tachykinins on the steady state Ca(++)-rise ([Ca++]i) in transfected chinese hamster ovary cells expressing recombinant human Neurokinin 2 (NK2) receptors. The rank order of potency with natural tachykinins was NeurokininA > Neurokinin B > Eledoisin > Physaelamin > substance P. The selective NK2 agonist, [beta-Ala8]NKA(4-10) was very potent, with an EC50 value of 4.83 x 10(-9) M whereas Senktide, MePhe7NKB and Sar9, (MetO2)11 substance P, selective NK3 and NK1 agonists, respectively, did not have any effect on [Ca++]i in hrNK2CHO cells, suggesting a selective and preferential recognition and activation of NK2 receptors in these cells. (+/-) SR 48968, a selective NK2 antagonist, abolished the beta-AlaNKA-induced [Ca++]i with an IC50 value of 0.7 nM. Two other peptidic NK2 antagonists, MEN 10376 and L-658977, were less active with IC50 values of 49 nM and 5.29 microM, respectively. In contrast, (+/-) CP-96,345 and (+/-)CP-99,994 and RP 67580, all selective NK1 antagonists, did not have any effect on the beta-AlaNKA-induced [Ca++]i in hrNK2CHO cells (+/-) SR 140333, a potent and selective NK1 antagonist, had a 35% inhibition under similar conditions. These data demonstrate a high selectivity and sensitivity to NK2 receptor mediated [Ca++]i in rhNK2R-CHO cells and may be of value as a rapid, selective test of drug action at the human NK2 receptors in vitro.
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PMID:Pharmacological characterization of tachykinin-induced intracellular calcium rise in a human NK2 receptor transfected cell line. 818 7

The effects of tachykinins on primary afferent neurons of bullfrog dorsal root ganglia (DRG) were examined by using whole-cell patch-clamp methods. Neurokinin A (NKA) caused inward current (INKA) in a concentration-dependent manner. Concentration-response curve showed that the EC50 for NKA was 6 nM. The INKA showed strong tachyphylaxis, when NKA was continuously applied for more than 1 min. Substance P (SP) also produced inward current with potency similar to that of NKA. Neurokinin B (NKB) was less effective in producing the inward current. The order of agonist potency was NKA = SP >> NKB. Spantide ([D-Arg1, D-Trp7.9, Leu11]SP), a non-selective peptide antagonist at tachykinin receptors, reduced the tachykinin-induced current. CP-99,994, a selective non-peptide antagonist for neurokinin-1 (NK1) receptor, inhibited the inward currents produced by NKA and SP. The INKA was associated with decrease in K+ conductance. NKA suppressed both a voltage-dependent K+ current, the M-current (IM), and a voltage-independent background K+ current, IK(B). Intracellular dialysis with GTP gamma S (100 nM) or GDP beta S (100 microM) depressed the INKA. Pre-treatment of DRG neurons with pertussis toxin (PTX) did not prevent the INKA. Depletion of intracellular ATP depressed the INKA. These results suggest that the tachykinin-induced inward current is mediated through the NK1 receptor which mainly couples to PTX-insensitive G-protein in bullfrog primary afferent neurons.
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PMID:Tachykinins cause inward current through NK1 receptors in bullfrog sensory neurons. 872 87

The occurrence of inflammation as indicated by extravasation of Evans blue bound to plasma proteins was examined in various parts of the gastrointestinal tract in the rat, following administration of tachykinins, capsaicin and hydrochloric acid. Intravenous neurokinin A dose-dependently induced extravasation in stomach, duodenum, jejunum, caecum and colon, but had no effect in ileum. Neurokinin B equipotently induced extravasation in the stomach but had no effect in other parts of the gut and substance P had no effects on extravasation of Evans blue in any of the examined parts of the gastrointestinal tract. Capsaicin given intraperitoneally increased vascular permeability in stomach and duodenum only, while extravasation of Evans blue after capsaicin given intraluminally did not differ from the effect of the vehicle alone. As a comparison, HCl given intraluminally in the duodenum was found to induce a prominent extravasation of Evans blue of a greater magnitude than than of tachykinins. We suggest that tachykinins, and in particular neurokinin A, may be of importance for extravasation of plasma proteins as part of inflammatory reactions in the upper and lower gastrointestinal tract.
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PMID:Tachykinins increase vascular permeability in the gastrointestinal tract of the rat. 873 55

Intracellular current-clamp recordings were performed using in vitro brainstem slice preparations to compare the actions of substance P, neurokinin A, neurokinin B and their agonists on rat dorsal vagal nucleus neurons with or without antagonists of neurokinin 1 and 2 receptors. The agonists used were either [Sar9,Met(O2)11]substance P or septide for neurokinin 1 and [Nle10]neurokinin A(4-10) for neurokinin 2 receptors. The antagonists were spantide, SR 140333 or RP 67580 for neurokinin 1 receptors and SR 48968 for neurokinin 2 receptors. Identification of vagal neurons was achieved electrophysiologically by testing antidromic responses and confirmed morphologically by an intracellular injection of biocytin. Of the 70 neurons tested, substance P led to depolarization in 36, hyperpolarization in six and no effect in 28. Depolarization was concentration dependent and generally associated with an increase of the membrane input resistance. Addition of tetrodotoxin (1 microM) to the medium had no effect on depolarization. RP 67580 (1 microM) blocked depolarization, but spantide and SR 140333 (microM to 50 microM) did not. Hyperpolarization was never observed using agonists. Neurokinin A and neurokinin 2 agonist induced concentration-dependent depolarization associated with an increase in membrane input resistance in eight of 14 neurons and in four of nine neurons, respectively. Depolarization was only partially abolished by the neurokinin 2 antagonist SR 48968. Neurokinin B had no effect in any of the eight neurons tested. These data prove that vagal neurons have neurokinin 1 and 2 receptors and that tachykinin could produce either depolarization or hyperpolarization. Since membrane potential variations were associated with an increase (during depolarization) or decrease (during hyperpolarization) in the membrane input resistance and since the reversal potential was close to the potassium equilibrium potential, we speculate that these effects are mediated by modulation of potassium conductance.
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PMID:Effects of tachykinins on identified dorsal vagal neurons: an electrophysiological study in vitro. 883 96

The neuroprotective effect of tachykinins against excitotoxic death of cholinergic neurons was studied in rat striatal cell cultures. Quinolinic acid (QUIN) and kainic acid (KA) produced a dose dependent decrease in choline acetyltransferase activity, but KA was more potent. Our results show that substance P (SP) totally reversed the toxicity induced by 125 microM QUIN but not by 40 microM KA. This effect was also observed using protease inhibitors or a SP-analog resistant to degradation, [Sar9]-Substance P. The survival of neuron specific enolase- and acetylcholinesterase (AChE)-positive cells after treatment with QUIN alone or in the presence of SP was also examined. We observed that, while a decrease in total cell number produced by QUIN was not prevented by SP treatment, AChE-positive cells were rescued from the toxic damage. To characterize the SP protective effect we used more selective agonists of the three classes of neurokinin (NK) receptors. [Sar9, Met(O2)11]-Substance P (NK1 receptor agonist), [Nle10]-Neurokinin A (NK2 receptor agonist) or [Me-Phe7]-Neurokinin B (NK3 receptor agonist) were all able to block the toxic effect of QUIN on cholinergic activity. These results show that tachykinins provide an important protective support for striatal neurons, suggesting a possible therapeutical benefit in neurodegenerative disorders affecting cholinergic neurons.
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PMID:Tachykinins protect cholinergic neurons from quinolinic acid excitotoxicity in striatal cultures. 897 30

The effects of substance P and related tachykinins on intrinsic membrane properties and synaptic responses of neurons in cortical slices were determined. Substance P had no detectable effect on membrane properties of principal neurons in layer II or V of the rat medial entorhinal cortex or on neurons in either layer of the anterior cingulate cortex. Specific agonists at the neurokinin1-receptor were also without effect as were agonists at both neurokinin1- and neurokinin3-receptors. Substance P hyperpolarized a small number of principal neurons. These responses were weak and desensitized with repeated applications. Similar effects were seen with other neurokinin1-receptor agonists. Excitatory synaptic potentials mediated by either alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- or N-methyl-D-aspartate-receptors in principal neurons of the entorhinal cortex were unaffected by substance P. Responses of entorhinal neurons to iontophoretically applied glutamate and N-methyl-D-aspartate were also unaffected. Inhibitory synaptic potentials mediated by either GABA(A)- or GABA(B)-receptors in entorhinal neurons were slightly but consistently enhanced by substance P. Neurons identified as interneurons on the basis of their firing characteristics were consistently depolarized by substance P. These responses also desensitized with repeated applications. Spontaneous epileptiform discharges evoked in entorhinal cortex by perfusion with a GABA(A)-receptor antagonist (bicuculline), were reduced in frequency and, sometimes, in duration by substance P. This effect was mimicked by other neurokinin1-receptor agonists and blocked by neurokinin1-receptor antagonists. It was also mimicked by neurokinin A but not by a specific neurokinin1-receptor agonist. The reduction in frequency of discharges was also mimicked by a GABA(B)-receptor agonist, L-baclofen, and blocked by the GABA(B)-receptor antagonist, CGP55845A. Neurokinin B, and a specific neurokinin1-receptor agonist (senktide), increased the frequency and (sometimes) duration of epileptiform discharges. Substance P could also increase frequency but this usually succeeded or preceded a decrease in frequency. The effect of neurokinin B was reduced by a metabotropic glutamate receptor antagonist. Substance P appears to have little direct effect on principal neurons of the entorhinal cortex but may hyperpolarize them indirectly by activating interneurons and releasing GABA. This indirect inhibition may be responsible for the ability of substance P to reduce the frequency of epileptiform discharges in the entorhinal cortex and may suggest that neurokinin1-receptor agonists have potential as anticonvulsant drugs.
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PMID:Tachykinins may modify spontaneous epileptiform activity in the rat entorhinal cortex in vitro by activating GABAergic inhibition. 950 45


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