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)

Substance P or the substance P receptor antagonist (D-Arg1,D-Trp7.9,Leu11)-substance P (Spantide) was injected into the lumbar subarachnoid space in mice, and the ability to change the tail-flick reflex and the tail skin temperature was investigated. Tail-flick latency (the time needed to evoke the tail-flick reflex by noxious radiant heat) was reduced for 1-4 min after intrathecal administration of substance P (5 micrograms), but the tail skin temperature was not significantly changed. Nor was the tail skin temperature significantly changed after intrathecal injection of Spantide (5 micrograms), but this compound significantly increased tail-flick latencies 5-30 min after injection. Analysis of co-variance showed that the effects of substance P or Spantide on tail-flick latency were significant, whereas the influence of tail skin temperature on tail-flick latency was non-significant. Thus, intrathecal substance P induces a short-lasting increase in nociceptive sensitivity, and intrathecal Spantide produces an antinociceptive effect of longer duration. The results seem not to be the result of changes in tail skin temperature.
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PMID:Effects of intrathecal substance P and a substance P antagonist on a reflex to noxious heat are independent of changes in tail skin temperature. 170 12

Recently, two compounds have been developed, designated septide and senktide, which are highly selective agonists for the substance P receptor, types NK-1 and NK-3, respectively. Each of these, when injected intrathecally in awake rats, produced a distinct and non-overlapping constellation of sensory and behavioural effects which were subsets of the symptoms evoked by intrathecal administration of substance P. Prior systemic administration of 5-hydroxytryptamine (5-HT), alpha-adrenergic and opiate receptor antagonists, at doses sufficient to block the behavioural effects of the corresponding receptor agonists, did not alter responses to intrathecally injected septide or senktide. This was so, even for symptoms which suggested inhibitory mediation, hypoalgesia and (transient) motor flaccidity. Septide and senktide, administered by lumbar puncture and by indwelling catheter, produced identical results. Finally, in contrast to some other peptides, flaccid paralysis induced by senktide was not accompanied by spinal necrosis.
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PMID:Neurochemical mediators of the behavioural effects of receptor-selective substance P agonists administered intrathecally in the rat. 170 12

Autoradiography was used to localize and quantify substance P receptors in the feline gastrointestinal tract. The specific binding of 125I-Bolton Hunter substance P was determined in the esophagus, lower esophageal sphincter, antrum, pylorus, duodenum, jejunum, ileum, ileocecal sphincter, and colon. Competitive binding studies indicated that substance P binding sites or NK-1 receptor sites were demonstrated. The concentration of NK-1 receptors was greatest in the distal half of the gastrointestinal tract, with the highest concentrations in the proximal colon. The circular muscle layer contained the greatest amount of substance P binding. The location and density of binding sites for substance P may be important in understanding the relative importance of both the pharmacological responses to this neuropeptide and the immunohistochemical evidence of the peptide at different sites in the intestine.
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PMID:Distribution and density of substance P receptors in the feline gastrointestinal tract using autoradiography. 170 47

Two members of a new class of non-peptide antagonists of substance P, (+-)-cis-3-(2-methoxybenzylamino)-2-benzhydrylquinuclidine [(+/-)-CP-96,345; I] and (+-)-cis-3-(2-chlorobenzylamino)-2-benzhydrylquinuclidine [II], were tested for their ability to antagonize neurokinin-induced contractions of the rabbit cava and jugular veins (NK-1), the rabbit pulmonary artery (NK-2) and the rat portal vein (NK-3 system). Compound 1 is the most potent NK-1 receptor antagonist identified until now; its apparent affinity (pA2 = 9.52) is at least two log units higher than those of other NK-1 antagonists. Compound II is less active. Both compounds have been found to be almost inactive as NK-2 and NK-3 antagonists and should, therefore, be considered as selective for the NK-1 receptor. The new compounds have no direct myotropic effects and are specific for neurokinin (NK-1) receptors since they do not affect the myotropic effects of angiotensin, noradrenaline and bradykinin in the rabbit cava and jugular veins.
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PMID:Selectivity and specificity of new, non-peptide, quinuclidine antagonists of substance P. 170 18

The vasomotor responses of tachykinins have been studied in the cerebral vasculature of human, pig, cat, and guinea pig. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and neuropeptide K (NPK) induced concentration-dependent relaxations of precontracted cerebral arteries in all species when examined by a sensitive in vitro technique. In addition, the relaxant responses to SP, NKA, and NKB were studied in cat pial arterioles by peptide microapplication in situ. In human pial vessels, the order of relaxant potency was SP greater than NKB greater than NKA greater than NPK; in the pig middle cerebral artery, there was no difference in potency between the tachykinins; in the cat middle cerebral artery, SP = NKB greater than NKA = NPK; and in the guinea pig basilar artery, SP much greater than NPK = NKA greater than NKB. Responses induced by SP, NKA, and NKB in the cat were comparable in vitro and in situ. Removal of the endothelium abolished relaxation induced by all four tachykinins. The relaxant responses of guinea pig basilar arteries to SP, NKA, and NPK were competitively antagonized by the SP antagonist Spantide. However, Spantide lowered the Imax of the NKB concentration-response curve without any rightward shift, suggesting action at a different site than the other tachykinins. In the guinea pig basilar artery, the relaxation seems to be exerted via a NK-1 receptor subtype while the receptor subtype is more unclear in cerebral arteries from human, cat, and pig.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tachykinins (substance P, neurokinin A, neuropeptide K, and neurokinin B) in the cerebral circulation: vasomotor responses in vitro and in situ. 171 Oct 51

The analogues [Glu(OBzl)11]SP6-11 and [Glu(OBzl)11]SP5-11 of the C-terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the SCH3 group of Met11 is replaced by the COOCH2C6H5 group. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD), and rat portal vein (RPV). The selectivity for the different receptors has been studied by utilizing atropine-treated guinea pig ileum (GPI + At). The results showed that both analogues are mainly active on GPI through the NK-1 receptor and that both analogues are equipotent to Substance P.
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PMID:Synthesis and biological activity of substance P C-terminal hexapeptide and heptapeptide analogues. 171 23

Substance P (SP) stimulates polyphosphoinositide breakdown in the rat anterior pituitary through an NK-1 receptor. In the present study we present evidence that the coupling between the SP-NK1 receptor complex and polyphosphoinositide-specific phospholipase C (PI-PLC) in rat anterior pituitary membranes may involve a mechanism consistent with a GTP-binding protein. The formation of inositol phosphates from [3H]myo-inositol-labelled anterior pituitary membranes induced by SP was potentiated by GTP and non-hydrolysable guanine nucleotides. The stimulatory effects of SP alone and SP plus GTP could be blocked by addition of GDP-beta-S (guanosine 5-O-(thiodiphosphate] in excess. Basal and SP plus guanine nucleotide-induced inositol phosphate formation were stimulated by fluoride, whereas the effect of SP alone was inhibited. Pretreatment of anterior pituitary membranes with sodium deoxycholate attenuated the inositol phosphate response elicited by GTP and GTP-gamma-S, whereas basal and SP-stimulated inositol phosphate production showed a peak at 1 mg sodium deoxycholate/ml. SP, fluoride and guanine nucleotide stimulatory effects on hydrolysis of polyphosphoinositide (PPI) were unaffected by pretreatment of anterior pituitary cells with cholera or pertussis toxin for 12h. Treatment of anterior pituitary membranes with cholera and pertussis toxin yielded [32P]ADP-ribosylation of two proteins with molecular masses of 45 and 41 kDa respectively. We conclude that SP coupling to PI-PLC through the NK1 receptor in the rat anterior pituitary involves a GTP-binding mechanism distinct from the G-proteins associated with adenylate cyclase, Gs and Gi.
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PMID:Substance P stimulation of polyphosphoinositide hydrolysis in rat anterior pituitary membranes involves a GTP-dependent mechanism. 171 80

Substance P (SP) stimulated [3H]taurine release from human astrocytoma cells (U-373 MG). This effect was concentration dependent and the EC50 was 0.3 nM. This stimulatory effect of SP can be inhibited by spantide, a SP receptor antagonist. The rank order of potencies of related tachykinins and their analogues in stimulating the release of [3H]taurine was SP much greater than neurokinin A much greater than neurokinin B and [Glp6,L-Pro9]SP (6-11) much greater than [Glp6, D-Pro9]SP (6-11) which conformed to that reported for the tachykinin NK-1 receptor. In addition to SP, isoproterenol, a beta-adrenergic agonist, can also increase the release of [3H]taurine from these cells and the effects of SP and isoproterenol were additive.
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PMID:Effects of tachykinins on [3H]taurine release from human astrocytoma cells (U-373 MG). 171 6

We compared the ability of spantide I and II to antagonize tachykinins in monoreceptor bioassays. Both peptides antagonized the response to substance P methylester in the guinea-pig ileum (NK-1 receptor-mediated) with greater affinity than the responses mediated by NK-2 or NK-3 receptors in other bioassays. Spantide II was about 10 times more potent than spantide I as an NK-1 antagonist and also possessed some selectivity for the NK-2 receptor subtype present in the hamster trachea. Spantide II is a suitable tool to assess the role of NK-1 receptors in the central and peripheral nervous system.
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PMID:Activity of spantide I and II at various tachykinin receptors and NK-2 tachykinin receptor subtypes. 171 73

We have used novel selective agonist ligands to examine neurokinin receptors mediating the contractile response to tachykinins in the rabbit iris sphincter preparation in vitro. The selective NK-1 receptor agonist delta-amino valeryl-[L-Pro9,N-Me Leu10]SP-(7-11) (GR73632) and the NK-3 receptor-selective agonist succ-[Asp6,N-Me-Phe8] SP-(6-11) (senktide) were both very active (concentration range 0.032 pM-10 nM and 0.1 pM-32 nM respectively), and were 933 and 16.6 times more potent than substance P, respectively, in contracting the iris. In contrast, the NK-2 selective agonist [Lys3,Gly8-R-gamma-lactam,Leu9]NKA-(3-10) (GR64349) was active only at the highest concentrations tested (3.2 nM-32 microM), and had 0.054 the activity of substance P. The presence of several peptidase inhibitors was without effect on the concentration-response relationship to substance P, GR73632, GR64349 or senktide. Tachykinins differed in their offset kinetics. Responses to GR73632, GR64349 and senktide were rapid in offset (times to reach half maximal responses were 1.5, 1.1 and 5.1 min, respectively), whereas responses to substance P were very much more prolonged in duration (time to reach half maximal response was 35.3 min). These results suggest the presence of both NK-1 and NK-3 receptors mediating contraction of the rabbit iris sphincter preparation. In addition, differences in response offset kinetics seem not to be due to differences in peptide metabolism, and suggest a property of substance P not shared by the other tachykinins used in this study.
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PMID:Neurokinin receptors in the rabbit iris sphincter characterised by novel agonist ligands. 171 75


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