UNIPROT:P20366 - FACTA Search

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)

Various procedures for extraction at acid, neutral and alkaline pH were compared with regard to the yield of different tachykinins and tachykinin-like substances from rat spinal cord. Reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay with various C-terminally directed tachykinin antisera and a newly developed N-terminally directed substance P (SP)-antiserum (SPN 1) were used. Antiserum SPN 1 fully reacts with SP-analogues modified at the C-terminal end (SP free acid and SP-Gly-Lys) and also (77%) with SP(1-9) but not with C-terminal SP-fragments lacking 2 or more N-terminal amino acids. The highest levels of SP-like immunoreactivity (LI) and neurokinin A (NKA)-LI were measured after combined water and acetic acid extraction procedures. Also when measuring cholecystokinin-like immunoreactivity the highest level was obtained following this extraction procedure. RP-HPLC revealed a major component of SP-LI at the position of synthetic SP irrespectively of the extraction method and if the C- or N-terminally directed antiserum was used. Neutral water extracts contained a late eluting component detected with the C-terminally, but not with the N-terminally, directed antiserum. Acid and alkaline extracts, in contrast, contained components which could be detected with the N-terminally, but not with the C-terminally, directed SP-antiserum. Immunoreactive components eluting at the position of NKA and NKB were found in all types of extracts with NKA-, kassinin- and eledoisin-antisera. The NKB- and neuropeptide K (NPK)-components were more prominent in acid than in neutral and alkaline extracts. In conclusion, the present results indicate that rat spinal cord may contain molecular forms of tachykinin-like immunoreactivity in addition to those previously described and illustrate the importance of the choice of extraction method in immunochemical studies. Combined extraction in water and acetic acid appears to be a suitable method when the content of peptides with different chemical properties are to be measured in a tissue sample.
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PMID:Multiple molecular forms of tachykinins in rat spinal cord: a study comparing different extraction methods. 752 21

Actions of substance P (SP, 10(-9) to 10(-6) M), neurokinin A (NKA, 10(-9) to 10(-6) M) and neurokinin B (NKB, 10(-10) to 10(-6) M) in the circular muscle of guinea pig ileum were investigated in segment and strip preparations, in which methacholine produced similar contractions. In the segment preparations, three tachykinins produced repeatedly occurring twitch-like contractions. Their efficacies were similar with the same maximal contractions, but their potencies were different (NKB > NKA = SP). Latency (38 sec) was observed before the initiation of contractions in response to NKA, but not to SP or NKB. Atropine (10(-6) M) and tetrodotoxin (3 x 10(-7) M) did not affect NKA-induced contractions, but inhibited SP- and NKB-induced contractions; the dose-response curves for SP and NKB were rightwardly shifted by atropine. The treatment with atropine brought out latency in the responses for NKB. In the strip preparations, SP did not substantially induce concentrations, but NKA and NKB produced twitch-like contractions after latent periods of 28 and 36 sec, respectively. The efficacy of NKA was similar to that in segment preparations, while that of NKB was much lower in strip preparations. Unlike in segment preparations, atropine did not inhibit contractions induced by the two tachykinins in strip preparations. These results suggest that tachykinins induce contractions through myogenic and neurogenic mechanisms, the latter of which may be inoperative in strip preparations.
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PMID:Tachykinin-induced contractions in the circular muscle of guinea pig ileum. 752 85

1. The effects of the non-peptide tachykinin NK1 receptor antagonists, RP 67580, SR 140333, CP-96,345 and CP-99,994 have been investigated on electrically-evoked release of substance P-like immunoreactivity (SP-LI) from rat spinal cord slices. 2. RP 67580 (10 nM) and SR 140333 (1 nM), perfused 5 min prior to and during 8 min stimulation of the dorsal roots (20 V, 0.5 ms, 1 Hz), significantly enhanced SP-LI release by 213 +/- 43 (n = 8) and 203 +/- 31 (n = 5) % of control evoked release (187 +/- 16% of basal outflow, n = 22) respectively. Neither compound modified basal outflow of SP-LI (15.3 +/- 2.5 fmol/8 ml, n = 10). 3. RP 67580 (10 nM) did not modify electrically-evoked release of calcitonin gene-related peptide-LI from rat spinal cord slices. 4. CP-96,345 (10 nM) and CP-99,994 (1 and 10 nM) did not alter electrically-evoked SP-LI release; however, they both inhibited release at 1 microM. Inhibition was also induced by 1 microM RP 67580 but not 1 microM SR 140333. 5. The effect of the NK1 receptor agonists, [Sar9 Met (O2)11]SP and [Sar9]SP, could not be tested on SP-LI release due to interference with the substance P radioimmunoassay (RIA). The other NK1 receptor agonists used, GR 73632, [Pro9]SP and septide, which did not interfere with the RIA, increased SP-LI basal outflow by 1807 +/- 713% (n = 3), 1259 +/- 160% (n = 3) and 620 +/- 69% (n = 3) at 10 nM, 1 nM and 1 microM, respectively. At the same concentrations, the three agonists also enhanced electrically evoked SP-LI release by 204 +/- 38% (n = 6), 753 +/- 40% (n = 3) and 504 +/- 97% (n = 3), respectively. The GR 73632 (10 nM)-induced increase in electrically-evoked SP-LI release, was not prevented by SR140333 (100 nM). None of the agonists inhibited SP-LI release at lower concentrations (0.1 nM GR73632; 0.01 and 0.1 nM [Pro9]SP and 1-100 nM septide).6 NKA and NKB, at concentrations up to 10 nM which did not interfere with the RIA, did not modify electrically-evoked release of SP-LI.7 The ability of NKI receptor antagonists to enhance electrically-evoked SP-LI release supports the concept of an NK1 autoreceptor control mechanism at substance P nerve terminals within the dorsal horn of the rat spinal cord.
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PMID:Effect of the tachykinin NK1 receptor antagonists, RP 67580 and SR 140333, on electrically-evoked substance P release from rat spinal cord. 753 May 76

The annulus fibrosus of the human intervertebral disc is sparsely innervated, some of the fibers containing substance P. We could demonstrate, by autoradiography, binding sites for substance P localized on the endothelium of small blood vessels in the annulus fibrosus of human intervertebral discs removed during anterior fusion for back pain. In binding inhibition studies, binding of 125I-Bolton Hunter-substance P was inhibited by unlabeled substance P and the related tachykinins neurokinin A and neurokinin B with a rank order of potency substance P > NKA > NKB. Specific binding was reduced > 75 percent by 5'-guanylylimidodiphosphate, indicating G-protein coupling. These features are characteristic of an NK1 receptor through which vascular effects, i.e., vasodilation, plasma extravasation and angiogenesis of substance P, are mediated. The presence of NK1 receptors on blood vessels in the annulus fibrosus may indicate a role for substance P in tissue repair although acute proinflammatory effects may contribute to discogenic pain.
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PMID:Substance P in intervertebral discs. Binding sites on vascular endothelium of the human annulus fibrosus. 753 Aug 90

1. The distribution and characteristics of tachykinin NK1 binding sites have been compared in human and guinea pig lung using quantitative in vitro receptor autoradiography with [125I]-Bolton Hunter-labelled substance P ([125I]-BH-SP). In addition, the effects on these sites of ovalbumin sensitization and challenge have been determined in guinea pig lung. 2. [125I]-BH-SP bound specifically and with high affinity to microvascular endothelium in both human and guinea pig lung, but to bronchial smooth muscle and pulmonary artery media in only guinea pig lung. 3. Specific binding of [125I]-BH-SP to guinea pig bronchial smooth muscle was positively correlated with airway diameter in the range 150-800 microns and was less dense in trachea than in main bronchi. 4. [125I]-BH-SP binding was inhibited by tachykinins with rank orders of affinity of SP > NKA > NKB (human microvessels) and SP > NKA = NKB (guinea pig bronchi and pulmonary arteries). NKA displayed a higher affinity for [125I]-BH-SP binding sites in human microvessels than in guinea pig tissues (P < 0.0001), indicating differences in selectivity for tachykinins between human and guinea pig NK1 receptors. 5. In both human and guinea pig lung, [125I]-BH-SP binding was inhibited by the specific tachykinin receptor antagonists FK888 (NK1 selective antagonist) and FK224 (mixed NK1/NK2 antagonist), with FK888 displaying equal affinity to SP and > 500 times higher affinity than FK224. SP, NKA, NKB and FK888 exhibited similar affinities for [125I]-BH-SP binding sites in both guinea pig arteries and bronchi. 6. Similar distributions, densities and characteristics of [I251]-BH-SP binding sites were demonstrated in oval bumin-sensitized and -challenged guinea-pig lung and in naive animals.7. Differences in the distribution and characteristics of NKI binding sites labelled with [125I]-BH-SP between guinea pig and human lung suggest limitations in the use of guinea pig models for studying roles of tachykinins in pulmonary disease. However, the similar microvascular distributions of NK,binding sites in human and guinea pig lung suggest that the selective tachykinin receptor antagonistsFK888 and FK224 may be useful in the management of airway inflammation in man.
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PMID:Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung. 753 86

1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiotensin AT1 (losartan and its active metabolite EXP 3174), angiotensin AT2 (PD 123,319) or tachykinin NK3 (R 486) receptors. 2. I.c.v. administration of 25 pmol AII evoked an increase in mean arterial blood pressure (MAP) and water intake behaviour, accompanied by a transient bradycardia, whereas 25 pmol [MePhe7]NKB caused a transient increase in MAP and heart rate (HR) concurrently with marked wet dog shake behaviour. At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours. 3. Losartan (650 pmol, i.c.v.) reduced significantly the cardiovascular and behavioural responses to AII or [MePhe7]NKB, but not to SP or NKA. While 65 pmol losartan was inactive, 260 pmol inhibited selectively the central effects of AII. Whereas EXP 3174 (6.5 nmol) blocked both AII and [MePhe7]NKB-mediated responses, the dose of 650 pmol blocked only the responses to AII. 4. The central responses to AII and [MePhe7]NKB were not affected by PD 123,319 (650 pmol). On the other hand, the [MePhe7]NKB-induced central effects were significantly reduced by R 486 (650 pmol). The NK3-selective antagonist had no effect against AII. 5. This study provides functional evidence, to support earlier binding data, that losartan (and to some extent its active metabolite EXP 3174) interact with the tachykinin NK3 receptor in rat brain. However,the cardiovascular and behavioural responses induced by central tachykinin agonists (SP, NKA and[MePhe7]NKB) and All are mediated by unrelated mechanisms.
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PMID:Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat. 754 Dec 80

The tachykinins, substance P (SP) and neurokinins A (NKA) and B (NKB), have been identified in the respiratory tract and implicated in mediating neurogenic inflammation of the airways. To the extent that these neuropeptides may be involved in the pathogenesis of asthma, a condition associated with hyperplasia of airway smooth muscle (ASM), we examined the mitogenic effects and mechanisms of action of tachykinins in cultured rabbit ASM cells. SP was found to elicit dose-dependent (10(-14) to 10(-4) M) stimulation of ASM cell proliferation, with a mean (+/- SE) maximal increase in cell number of 169 +/- 6.1% of control. In contrast, NKA and NKB had little and no effect on ASM cell growth, respectively. Because SP is nonselective in its binding to the tachykinin receptors, to identify the specific NK receptor subtype(s) mediating the promitogenic action of SP, in separate studies we found that 1) the NK1-receptor-specific agonist, [beta-Ala4, Sar9, Met(O2)11]SP-(4-11) induced stimulation of ASM cell growth similar in magnitude to that elicited by SP; 2) in contrast, neither the NK1- nor NK2-receptor-specific agonists, [beta-Ala8]NKA-(4-10) and [MePhe7]NKB, respectively, had any effect on ASM cell growth; and 3) the promitogenic action of SP was inhibited by the NK1-receptor antagonist, GR-82,334. Moreover, in extended experiments, we found that the phospholipase C and phospholipase A2 inhibitors, neomycin and quinacrine, respectively, each inhibited SP-induced ASM cell proliferation by approximately 45%. Collectively, these observations provide new evidence that the tachykinin SP induces ASM cell proliferation, and that this action is mediated by transmembrane signaling coupled to selective activation of the NK1 receptor.
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PMID:Tachykinin regulation of airway smooth muscle cell proliferation. 757 67

The effects of SR142801, a nonpeptide tachykinin neurokinin (NK3) receptor antagonist, were investigated on the functional events linked to NK3 receptor activation by using Chinese hamster ovary (CHO) cells transfected with the human NK3 receptor. Radioligand binding conducted with [125I]iodohistidyl-[MePhe7]-NKB revealed a competitive inhibition by SR142801 and its (-)-antipode SR142806 with Ki values of 0.21 +/- 0.03 and 32.0 +/- 5.0 nM, respectively. NK3 agonists such as [MePhe7]-NKB and senktide stimulated inositol monophosphate formation with EC50 values of 2.0 +/- 1.4 and 2.1 +/- 0.7 nM, respectively. SR142801 antagonized the stimulatory effect of [MePhe7]-NKB (10(-8) M) with an IC50 of 14.3 +/- 2.6 nM and of senktide (10(-8) M) with an IC50 of 4.8 +/- 1.5 nM. The [3H]arachidonic acid release induced by either [MePhe7]-NKB (EC50 of 2.6 +/- 0.2 nM) or senktide (EC50 of 4.2 +/- 2.9 nM) also was inhibited by SR142801 with IC50 values of 16.1 +/- 0.5 and 8.0 +/- 1.7 nM, respectively. The cyclic AMP accumulation induced by 10(-7) M [MePhe7]-NKB (EC50 of 54 +/- 2 nM) also was antagonized by SR142801 with an IC50 value of 4.0 +/- 0.7 nM. These antagonistic effects were stereospecific and NK3 receptor specific because the (-)-antipode, SR142806, was much less effective than SR142801 in NK3 agonist-evoked responses, whereas the nonpeptide NK1 (SR140333) and NK2 (SR48968) receptor antagonists were almost inactive. The activity of SR142801 also was evaluated on the [Ca++]i increase induced by 10(-9) M [MePhe7]-NKB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional characterization of the nonpeptide neurokinin3 (NK3) receptor antagonist, SR142801 on the human NK3 receptor expressed in Chinese hamster ovary cells. 761 92

The binding characteristics of [3H]substance P ([3H]SP) were investigated in membranes prepared from rat cerebral cortex. Binding of [3H]SP reached equilibrium after 50 min at 25 degrees C and was saturable at 8 nM. Saturation data could be resolved into high affinity (equilibrium dissociation constant, Kd, 0.22 nM) and low affinity sites (Kd, 2.65 nM). The low affinity sites were more numerous than the high affinity sites, with a ratio of 4:1. The non-hydrolyzable GTP analogue GppNHp had no effect on binding, indicating that the high and low affinity sites are not guanine nucleotide-regulated states of the same (NK-1) receptor. The low affinity sites are unlikely to represent NK-3 receptors since coincubation with the selective NK-3 receptor agonist senktide did not alter the biphasic nature of [3H]SP binding. The rank order of potency for inhibition of [3H]SP (2 nM) binding was SP > or = [Sar9, Met(O2)11]-SP > or = physalaemin >> SP(3-11) > NP gamma = [Ala3]-SP > or = SP(4-11) > or = NPK > or = SP(5-11) > or = NKB approximately NKA >> SP(1-9), compatible with binding to an NK-1 site. N-terminal fragments and non-amidated analogues were ineffective competitors for [3H]SP binding. However, competition data for several peptides including substance P (SP) and the NK-1 selective agonist [Sar9, Met(O2)11]-SP could be resolved into two components.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two classes of binding sites for [3H]substance P in rat cerebral cortex. 767 11

The present study evaluated the sensitivity of spontaneously hypertensive (SHR) and of Wistar Kyoto (WKY) rats to the hypotensive effect of tachykinins (TKs). Eledoisin, substance P, and the NK-1-selective agonist [Sar9,Met(O2)11]substance P evoked a smaller hypotensive response in SHR than in WKY rats. The hypotensive effect of NKA was slightly smaller in SHR, but no significant strain difference was observed. The NK-2-selective agonist [beta Ala8]NKA(4-10) was a very weak hypotensive agent in WKY rats, while being completely inactive in SHR. The NK-3-selective agonists [Asp5,6,MePhe8]substance P(5-11) and [MePhe7]NKB did not modify blood pressure in both strains. Heart rate was essentially unmodified following the NK-3 agonists, while it was increased after injection of substance P, [Sar9,Met(O2)11]substance P, and neurokinin A, the increase being greater in WKY than in SHR. Surprisingly, eledoisin increased heart rate in SHR, but not in WKY rats, despite the greater hypotensive effect elicited in the latter strain. The present results confirm that the hypotensive effect of peripheral TKs is mediated by NK-1 receptors and show that SHR are less sensitive than WKY rats to this effect.
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PMID:Hypotensive effect of intravenous injection of tachykinins in conscious, freely moving spontaneously hypertensive and Wistar Kyoto rats. 768 Jan 31

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