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)

125I-Tyr8-substance P binding was examined in a plasma membrane enriched fraction from the circular muscle of canine small intestine. The binding was quick in onset, reversible and saturable to a single high affinity binding site; KD and maximum receptor concentration were 0.50 = 0.06 nM and 742 +/- 173 fmol/mg of protein, respectively. KD values from kinetic and saturation studies were in agreement. The rank order of potency of the tachykinins and related compounds in displacing this binding was consistent with that of a neurokinin (NK)-P (NK-1) type binding site. 125I-eledoisin did not bind specifically to these membranes and eledoisin was relatively ineffective in displacing the 125I-Tyr8 substance P. Kassinin was totally ineffective. Based on relative agonist potencies, the tachykinins appeared to contract the circular muscle of canine small intestine in vitro by a mechanism which also could be considered to be a NK-P (NK-1) type receptor. However, a comparison of data obtained by these two techniques suggests that the NK-P (NK-1) type binding site and the receptor(s) responsible for contractile responses are not identical. There were discrepancies in relative orders of potency and in absolute potencies. The simplest explanation is that there is also an NK-A (NK-2) receptor which is functional but not labeled by our ligands. Possible reasons for these discrepancies are discussed.
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PMID:Receptors for tachykinins in canine intestine circular muscle. 245 82

The relative contribution of NK-1, NK-2 and NK-3 receptors to the sialogogic response to i.v. tachykinins was investigated in urethane-anesthetized rats. [Pro9,Met(O2)11]substance P (SP), a selective NK-1 receptor agonist, was about 10 times more potent than SP itself and its action was unaffected by atropine pretreatment. On the other hand [Nle10]neurokinin A (NKA)-(4-10) and [MePhe7]neurokinin B (NKB), two selective agonists for NK-2 and NK-3 receptors, respectively, were ineffective.
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PMID:NK-1 receptors mediate the tachykinin stimulation of salivary secretion: selective agonists provide further evidence. 245 68

Intracellular recordings were made from myenteric neurons of the guinea-pig duodenum and the responses to local ejection of several substance P (SP) analogs were examined. It was found that senktide (succinyl-[Asp6,Me-Phe8]SP-(6-11)), a selective analog for the NK-3 (SP-N) receptor, was particularly effective in depolarizing the neurons. It was 20-100 times more potent than SP and about 1000-fold more potent than the selective analogs for the NK-1 (SP-P) receptor, which resides on muscle cells. The response to the peptides was prolonged (20-120 s), but in about 20% of the cells there was a fast, early depolarizing component (observed only with senktide). In most cases there was an increase in the input resistance of the cell during the slow depolarization. Together with the finding that the response reversed at about -90 mV, this indicates that the response is due to the closure of K+ channels. The results support the existence of an NK-3 (SP-N) receptor and provide direct information about the membrane mechanisms through which NK-3 agonists excite myenteric neurons.
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PMID:The actions of receptor-selective substance P analogs on myenteric neurons: an electrophysiological investigation. 246 Mar 60

We have demonstrated a high affinity specific binding of 125I-Bolton Hunter conjugate of substance P (125I-BHSP) to rat retina membranes. The binding was saturable and monophasic with a Kd of 0.2 nM and a Bmax of 290 fmol/mg protein. The rank order of potency of tachykinins and related analogues in inhibiting 125I-BHSP binding conformed to that of the NK-1 (identical to SP-P) tachykinin receptor, with SP greater than NKA greater than or equal to KAS greater than or equal to NKB and [Glp6, L-Pro9]SP(6-11) being 60 times more active than [Glp6, D-Pro9]SP(6-11). After neonatal monosodium glutamate (MSG) treatment, there was a marked reduction in the number but not binding affinity of 125I-BHSP binding sites in the retina. The same treatment had no effect on either the number or binding affinities of NK-1 sites in the salivary gland.
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PMID:Effects of neonatal monosodium glutamate treatment on substance P binding sites in the rat retina. 246 98

Neuropeptide K (NPK) is an N-terminally extended derivative of neurokinin A (NKA) that can be a final product in the posttranslational processing of beta-preprotachykinin. A rat salivation bioassay was used to demonstrate potent effects of NPK at low doses, while effects due to NKA were much weaker at higher doses. The rank order of potency of beta-preprotachykinin-derived peptides on salivation responses was NPK greater than substance P greater than NKA much greater than beta-preprotachykinin-(72-96)-peptide. The time course of the NPK response was longer than that observed with substance P. The responses elicited by NPK were blocked by the tachykinin antagonist [D-Pro2,D-Trp7,9]substance P but not by atropine. In peptide coinfusion studies, NPK strikingly potentiated the salivation responses elicited by substance P. NPK in vitro displayed a 100 times lower potency than substance P in displacing 3H-labeled substance P binding in submandibular gland membranes, a tissue rich in SP-P type (NK-1) receptors. The possible cellular mechanisms by which NPK stimulates salivary gland secretion are discussed. We conclude that NPK and substance P may be cotransmitters derived by posttranslational processing of beta-preprotachykinin.
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PMID:Neuropeptide K potently stimulates salivary gland secretion and potentiates substance P-induced salivation. 246 27

Whole mounts of guinea pig ileum submucosa were incubated with radiolabeled tachykinins, and binding sites were visualized using autoradiography. Very dense specific binding for [125I]-Bolton-Hunter substance P (BHSP) was observed over ganglia of the submucous plexus, with weaker binding over internodal strands. Dense specific binding was also seen over occasional strands of circular muscle, with weak binding over clumps of mucosa. Although very weak binding was seen over some large blood vessels, no binding was associated with smaller blood vessels. Localization of binding was absent in whole-mounts coincubated with 1 microM substance P, used to define nonspecific binding. Localization of BHSP-specific binding was also abolished in whole-mounts coincubated with 1 nM substance P, but not with 1 nM neurokinin B, suggesting that binding was probably to an NK-1 tachykinin receptor. In whole-mounts incubated in [125I]-iodohistidyl neurokinin A (INKA) or [125I]-Bolton-Hunter neurokinin B (BHNKB), no specific binding over ganglia was observed. These binding sites for BHSP are probably identical with the neuronal substance P receptors mediating mucosal ion transport.
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PMID:Localization of substance P binding sites in submucous plexus of guinea pig ileum, using whole-mount autoradiography. 246 91

1. Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 microM to 30 microM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2. The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle. 3. The relative potencies of substance P and its fragments SP2-11, SP3-11, SP4-11 and SP1-4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4. Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-L-lysine, is rapid, reaching completion in 10-20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6. The similar characteristics of histamine release induced by substance P, VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activation-secretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.
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PMID:Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells. 246 82

1. We have studied the effect of the sensory neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) on microvascular permeability in guinea-pig airways in vivo and investigated whether CGRP would potentiate the effect of SP. We used the extravasation of intravenously-injected Evans blue dye as an index of permeability. 2. The tachykinins SP, NKA and NKB (0.025-5.0 nmol kg-1, i.v.) significantly (P less than 0.05) increased extravasation of dye in a dose-related manner and with a similar pattern of distribution; they were most potent in the trachea and main bronchi, less potent in the larynx and intrapulmonary airways, and had little significant effect in the bladder. 3. SP was significantly more potent in causing extravasation of dye than NKA or NKB with ED50 values (nmol kg-1) in the range 0.04-0.1, depending on the airway level, compared with values in the range 0.3-0.7 for the neurokinins. 4. CGRP (0.0025-2.5 nmol kg-1, i.v.) had no significant effect on microvascular permeability and did not potentiate SP-induced extravasation of dye. 5. Each neuropeptide decreased mean arterial blood pressure, indicating vasodilatation, in a dose-related manner. Co-injection of CGRP and SP produced additive decreases in arterial pressure. 6. We conclude that, in guinea-pig airways, tachykinins increase microvascular permeability via tachykinin receptors of the NK-1 sub-type (indicated by an order of potency of SP greater than NKA = NKB) on endothelial cells. The response appears to be related to mechanisms in addition to vasodilatation. The relevance of the responses to the tachykinins in asthma is discussed.
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PMID:Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea-pigs. 246 89

Mast cells of human skin, but not lung, adenoids, tonsils, or intestine, release histamine in response to substance P, vasoactive intestinal polypeptide, and somatostatin. The substance P receptor of skin mast cells is not of the NK-1, NK-2 or NK-3 subtypes of smooth muscle. Time course and calcium dependency of release by peptides differed from anti-IgE. With anti-IgE, the molar ratios of histamine:PGD2:LTC4 generated by skin mast cells was 1,000:25:2, whereas with substance P these ratios were 1,000:1:0.1. Similar results were obtained with the other neuropeptides. The ability of peptides to stimulate skin mast cell histamine release suggests a mechanism whereby their release from dermal nerve endings is coupled to changes in microvasculature.
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PMID:Interaction of neuropeptides with human mast cells. 246 22

This study was initiated to characterize the receptors which mediate the cardiovascular responses elicited by the intrathecal (i.th.) administration of neurokinins (NK) in the conscious freely moving rat. The dose response profile for substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) was determined over 0.065-65 nmol doses of the peptides. After i.th. administration at the T8-T10 thoracic level, only SP elicited a dose dependent pressor response. However, all NK elicited a dose dependent increase in heart rate (HR), and the following rank order of potency was observed: SP greater than NKA greater than NKB. SP (6.5 nmol) produced cardiovascular responses markedly greater than an equimolar dose of any of the seven SP fragments which were studied. The C-terminal sequences SP (4-11), [pGlu5]SP (5-11), [pGlu6]SP (6-11), and SP (7-11), as a group were slightly more potent than the N-terminal fragments, SP (1-4), SP (1-7) and SP (1-9) which were almost inactive. The NK-1 receptor selective agonists [Pro9, Met(O2)11]SP and [beta-Ala4, Sar9, Met(O2)11]SP (4-11), produced pressor and positive chronotropic responses equal to or greater in intensity than SP. With up to 6.5 nmol of the NK-2 receptor selective agonist [Nle10]NKA (4-10), no dose dependent cardiovascular response was produced and the NK-3 receptor selective agonist senktide (succinyl-[Asp6, MePhe8]SP (6-11], produced neither a cardiac nor pressor response when 6.5 nmol was administered. These results are consistent with the hypothesis that, receptors of the NK-1 subtype mediate the cardiovascular responses evoked by the spinal action of NK.
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PMID:Spinal action of neurokinins producing cardiovascular responses in the conscious freely moving rat: evidence for a NK-1 receptor mechanism. 246 23


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