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)

beta-Amyloid peptide and spantide have previously been described to have trophic effects on hippocampal neurones in vitro. We report here that bombesin and [Pro9]-substance P also show a neurotrophic effect on cultured hippocampal neurones. The neurotrophic effect of spantide or a beta-amyloid fragment containing amino acids 25 to 35 was not blocked by addition of the NK1 receptor agonist, substance P or the nonpeptide NK1 antagonist, RP 67580. For the bombesin-related peptides, the antagonist [Tyr4-DPhe12]-bombesin also provokes a trophic response, but the agonist alytesin and the antagonist [Leu13-psi-(CH2NH) Leu14]-bombesin have no effect on neurite growth. These results suggest that the observed trophic responses are unlikely to be mediated by a classical NK1 or bombesin receptor.
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PMID:The trophic effect of beta-amyloid 25-35 peptide is not mediated by NK1 or bombesin receptors. 128 35

Neurokinins (NK) are a group of peptides that share a common C-terminal and play an important role in control of the motor functions of the mammalian gut. Neurokinin receptors such as NK1, NK2 are certainly present in any segment of gut, whereas the NK3 receptors are probably present in the ileum of the Guinea pig and duodenum of the rat. We measured gastrointestinal responses with natural NK and their very specific agonists to determine the probable receptors in the stomach and small intestine of Sprague-Dawley rats. After overnight fasting, the rats were intubated with a catheter to feed saline liquid meal that contained 10% charcoal. Simultaneously, various doses of NK ranged selected from 10(-10) and 10(-7) mol kg-1 included substance P (SP), neurokinin A (NKA), neurokinin B (NKB), septide, [Nle10]-NKA4-10, senktide, and vehicle were intraperitoneally injected. At 15 min after being fed test meal, the rats were sacrificed. Then we removed entire gut including the stomach to measure the total length of small intestine and transit length of the charcoal, from which the transit ratio was calculated. In comparison with ratios of rats treated with vehicle, the inhibited transit ratios for charcoal were seen among SP at 10(-10) mol kg-1, NKA at 10(-10) and 10(-7) mol kg-1, [Nle10]-NKA4-10 at 10(-7) mol kg-1, and senktide at all doses except 10(-8) mol kg-1. Enhanced transit ratios were seen for septide at the doses 10(-8) and 10(-7) mol kg-1. Likewise the mean total intestinal lengths of rats if they received various treatments of peptides except that rats treated with NKB had somewhat diminished length than those of vehicle-treated rats. Some natural NK and their very specific receptor agonists mainly inhibited rat gastrointestinal charcoal transits. We suggest the probable presence of NK1, NK2 and NK3 receptors in the small intestine and stomach including pylorus of the rat.
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PMID:The motor actions of natural neurokinins and their specific agonists on the gastrointestinal tract of the rat. 128 5

Stable CHO cell clones which selectively express all three rat tachykinin receptors were established by transfection. The binding of radiolabled substance P and neurokinin A (substance K) to CHO clones expressing the NK1 and NK2 receptors, respectively, were saturatable and of high affinity (Kd = 0.17 nM (NK1); 3.4 nM (NK2)). Scatchard analysis of the binding data indicated for both receptors binding to a single population of binding sites, and competition binding studies showed that the binding specificities of the receptors corresponded to those of classical NK1 and NK2 receptors. In contrast, the binding of eledoisin to the NK3 receptor expressed in the transfected CHO cells was of low affinity (IC50 = 240 nM) compared to the high affinity of the receptor found when it was transiently expressed in COS-7 cells (IC50 = 8 nM). However, in both cases the receptor exhibited the specificity of a classical NK3 receptor. The established cell clones may provide an important tool for further analysis of the molecular mechanisms involved in binding, activation, and coupling of receptors for tachykinin peptides.
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PMID:Stable expression of high affinity NK1 (substance P) and NK2 (neurokinin A) receptors but low affinity NK3 (neurokinin B) receptors in transfected CHO cells. 131 Dec 70

Several neurokinins, namely substance P, neurokinin A, neurokinin B, [beta-Ala8]neurokinin A-(4-10) and senktide, were tested on noradrenaline-precontracted rabbit aortic rings to characterize the receptor mediating their endothelium-dependent relaxant effect in this preparation. CP-96,345, the new nonpeptide antagonist selective for the NK1 receptor, was also studied. Substance P, neurokinin A and neurokinin B, in that order of potency, were effective in relaxing precontracted rings, indicating the involvement of the NK1 receptor; [beta-Ala8]neurokinin A-(4-10) and senktide, which are selective agonists for NK2 and NK3 receptors, respectively, had no significant relaxant effect. The relaxant effects of substance P, neurokinin A and neurokinin B were competitively antagonized by nanomolar concentrations of CP-96,345. These findings support the view that the NK1 receptor mediates the endothelium-dependent relaxant effect of the neurokinins in rabbit aorta.
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PMID:Endothelium-dependent relaxant effect of neurokinins on rabbit aorta is mediated by the NK1 receptor. 131 13

Experiments were designed to characterize receptor(s) that mediate nonadrenergic, noncholinergic contractions of the guinea pig hilar bronchus using selective neurokinin (NK)1 (CP 96,345) and NK2 (R396 and MEN 10,376) tachykinin receptor antagonists. Left and right hilar bronchi were studied as pairs in the presence of atropine, propranolol, phentolamine; indomethacin and thiorphan. (2S, 3S)-cis-2-(diphenylmethyl)-N-(2-methoxyphe nyl)-1-azabicyclo[2,2,2]octan-3-amine (CP 96,345) selectively antagonized contractions of the bronchus to the NK1 agonist Ac-[Arg6,Sar9,Met(O2)11]-SP(6-11) with a -log molar KB value of about 8.0. Similarly, Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2 (R396) and [Tyr5, D-Trp6,8,9, Lys10]-NKA(4-10) (MEN 10,376) selectively antagonized contractions to the NK2 agonist [beta Ala8]-NKA(4-10) with -log molar KB values of about 5.5 and 6.7, respectively. CP 96,345 (3 x 10(-7) M) had no effect on contractions evoked by transmural electrical stimulation (TES). However, both R396 (1 x 10(-5) to 1 x 10(-4) M) and MEN 10,376 (1 x 10(-6) to 1 x 10(-5) M) caused blockade of responses to TES. CP 96,345 (3 x 10(-7) M) antagonized TES-induced contractions only when studied after substantial blockade by R396 or MEN 10,376. Contractions to TES were not abolished by R396, MEN 10,376 or a combination of these antagonists with CP 96,345. R396 (1 x 10(-6) M) increased the maximum contraction to TES and potentiated the frequency-response curve in bronchi treated with MEN 10,376 (1 x 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonadrenergic, noncholinergic contractile responses of the guinea pig hilar bronchus involve the preferential activation of tachykinin neurokinin2 receptors. 132 30

1. The tachykinin receptor mediating contraction of the guinea-pig isolated proximal urethra has been characterized by use of receptor selective agonists and antagonists. All experiments were performed in the presence of peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each) in order to reduce peptide degradation. 2. The natural tachykinins, substance P and neurokinin A produced a concentration-dependent contraction of rings of the proximal urethra which approached the same maximum (about 50% of the response to 80 mM KCl). Substance P (EC50 155 nM) was slightly (3.6 times) more potent than neurokinin A (EC50 560 nM). 3. The tachykinin NK1 receptor selective agonist, [Sar9]substance P sulphone (EC50 62 nM), was slightly more potent than substance P and produced the same maximal response of natural tachykinins. The NK2 receptor selective agonist, [beta Ala8] neurokinin A(4-10), was active only at microM concentrations and its maximal effect did not exceed 20% of that to substance P or neurokinin A. The NK3 receptor selective agonist, senktide, was ineffective up to 30 microM. 4. The response to [Sar9]substance P sulphone was antagonized in a competitive manner by either (+/-)-CP 96,345 (pA2 7.75, slope - 1.10) or GR 82,334 (pA2 7.31, slope - 1.26), which are selective NK1 receptor antagonists, while it was unaffected (up to 10 microM) by MEN 10,376, a selective NK2 receptor antagonist. 5. The response to 10 microM [beta Ala8]neurokinin A (4-10) was abolished by either 0.2 microM (+/-)-CP 96,345 or 1 microM GR 82,334, suggesting the involvement of NK1 receptors.6. Electrical field stimulation (5 and 10 Hz, 0.25 ms, 100 V, trains of 5 s duration) produced tetrodotoxin-sensitive phasic contractions of the urethra which were abolished by atropine plus phentolamine (3 microM each). Capsaicin (1 microM) produced a small transient contraction of the urethra which was abolished by ( )-CP 96,345 (0.1 microM). ( )-CP 96,345 did not modify the response to electrical field stimulation.7. We conclude that tachykinin NK, receptors are the main if not the only mediators of the contractile response of guinea-pig proximal urethra to peptides of this family and that this preparation is useful for assessing the affinities of various ligands for the NK, receptor. Endogenous tachykinins released from peripheral endings of capsaicin-sensitive primary afferents produce urethral contraction by activating NK, receptors.
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PMID:Tachykinin NK1 receptor in the guinea-pig isolated proximal urethra: characterization by receptor selective agonists and antagonists. 132 90

In the presence of atropine and guanethidine, the electrically evoked contractile response of the rabbit iris sphincter muscle is mediated by tachykinins. Two highly selective NK1 receptor antagonists, (+/-) CP-96,345 and spantide II, concentration dependently inhibited the contraction with pIC50 values of 5.4 and 6.1, respectively. A highly selective NK2 receptor antagonist, actinomycin D, was inactive, while another NK2 receptor antagonist of moderate selectivity, MEN 10,376, produced a slight inhibition of the contraction at high concentrations. Our results suggest that the electrically evoked, tachykinin-mediated contractile response of the rabbit iris sphincter muscle involves NK1 receptors only.
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PMID:The electrically evoked, tachykinin-mediated contractile response of the isolated rabbit iris sphincter muscle involves NK1 receptors only. 132 15

CP-96,345, a novel non-peptide antagonist of the NK1 receptor, at 10(-8)-10(-6) M decreased the frequency of peristalsis and reduced peristalsis-associated longitudinal muscle contractions in isolated guinea pig ileum. In the presence of 10(-6) M CP-96,345, further addition of 10(-6) M atropine blocked the peristalsis. When 10(-6) M atropine was first applied, more than half of the preparations developed atropine-resistant peristalsis. CP-96,345 at 10(-6) M blocked the atropine-resistant peristalsis. These results are consistent with the view that substance P is involved in the peristalsis in guinea pig ileum.
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PMID:Effects of CP-96,345, a novel non-peptide antagonist of NK1 receptor, on the peristalsis in isolated guinea pig ileum. 132 36

Amyloid beta protein (25-35) failed to significantly interact with tachykinin NK1 (rat forebrain, guinea-pig ileum) NK2 (rabbit pulmonary artery, hamster trachea) or NK-3 (guinea-pig cortex) receptors, as determined by radioligand binding and functional assays. A weak interaction (Ki 14.8 microM) was detected with NK2 receptors in rat small intestine. It appears unlikely that direct interaction with tachykinin receptors may account for the reported ability of amyloid beta protein (25-35) to affect neuronal survival.
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PMID:Interaction of amyloid beta protein (25-35) with tachykinin receptors. 132 24

Binding sites for [125I]-Bolton-Hunter substance P (BHSP) were investigated in homogenates of rat submandibular gland, colon smooth muscle, and urinary bladder. In vehicle-treated animals, the equilibrium dissociation constant (KD) was similar for both submandibular gland (0.46 +/- 0.03 nM) and colon (0.57 +/- 0.04 nM), although the maximum density of binding sites (Bmax) was about six-fold higher in submandibular gland compared with colon. These binding parameters remained unchanged in capsaicin-pretreated animals (140 mg/kg IP). In contrast, capsaicin pretreatment reduced (p less than 0.05) the Bmax in urinary bladder by twenty-five percent (0.56 fmol/mg wet weight) when compared to vehicle-treated controls (0.73 fmol/mg wet weight), although the KD was unchanged (vehicle, 0.29 +/- 0.08 nM; capsaicin, 0.24 +/- 0.04 nM). These data demonstrate that the NK1 receptors in submandibular gland and colon smooth muscle are not associated with or dependent upon intact primary afferent sensory neurons. However, a minority of NK1 receptors in the urinary bladder were lost after capsaicin, indicating that these receptors are located on sensory terminals, or may be dependent on growth factors or other chemicals released from these nerves.
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PMID:Effect of chronic capsaicin treatment on tachykinin NK1 binding sites in the rat. 132 47


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