UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vascular effects of PGE2, PGF2alpha and latanoprost acid on isolated bovine long posterior ciliary arteries and episcleral veins have been investigated using a small vessel myograph. PGE2 caused vasorelaxation both in the ciliary artery and episcleral vein (EC50: 7.9x10(-9) M and 2.1x10(-8) M respectively). Blockade of thromboxane receptors with GR 32191B, a TP receptor antagonist, shifted the concentration-response curves to the left in both preparations, probably indicating a slight co-stimulation of TP receptors in these vessels. Blockade of tachykinin NK-1 receptors had no effect on the PGE2 concentration-response curve. PGF2alpha caused a concentration dependent contraction in half of the ciliary arteries examined and relaxation in the other half. In the presence of the thromboxane receptor antagonist (GR 3211B) PGF2alpha always induced relaxation of the ciliary artery (EC50:1.3x10[-5] M). At higher concentrations PGF2alpha tended to slightly constrict the episcleral veins, but in the presence of the TP receptor antagonist (GR 32191B) only relaxation was observed. Latanoprost acid contracted the ciliary artery at concentrations above 10(-6) M. This effect was completely abolished by the TP receptor antagonist (GR 32191B). In the episcleral vein latanoprost acid induced a slight relaxation but in the presence of the TP receptor antagonist (GR 32191B) no effect was observed. These results indicate that PGE2 invariably induces vasorelaxation of bovine ciliary arteries and episcleral veins, whereas both PGF2alpha and latanoprost acid at high concentrations can cause vasoconstriction probably by stimulating TP receptors. PGF2alpha causes marked relaxation of both ciliary arteries and episcleral veins in the presence of the TP blocker which seems unlikely to be mediated by FP receptors.
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PMID:Effects of prostaglandin E2, F2alpha, and latanoprost acid on isolated ocular blood vessels in vitro. 957 37

The effects of the non-mammalian tachykinin physalaemin were studied on the short circuit current (SCC) and on both influx (Ji) and outflux (Jo) of 36Cl- and 22Na+ across the isolated skin of Rana esculenta. Physalaemin, added to the internal bathing fluid, increased SCC in a dose-dependent manner with a maximal effect at 1 microM. This increase was due to a stimulation of both Na+ absorption and Cl- secretion. Bumetanide (20 microM in the internal fluid), an inhibitor of the Na+/K+/2Cl- cotransporter, reduced the action of physalaemin on SCC by 46%. Furthermore diphenylamine-2-carboxylic acid (DPC, 0.1 mM in the external fluid), an inhibitor of Cl- channels, decreased the effect of the peptide on SCC by 48%. It is concluded that physalaemin activates the Na+/K+/2Cl- cotransporter at the basolateral membrane, accumulating Cl- in the cells and favouring its exit through Cl- channels at the outermost membrane of the epithelium. An inhibitor of cyclooxygenases, i.e. naproxen, strongly inhibited the physalaemin effect on SCC, whereas 5,8,11-eicosatriynoic acid (ETI), an inhibitor of lipooxygenases was without effect. Therefore, it is proposed that prostaglandins (probably PGE2) are the cellular mediators of this action. An antagonist of NK1 receptors for tachykinins, CP 99,994, inhibited the physalaemin action on SCC, whereas challenge with SR 48,968, an antagonist of NK2 receptors, had no effect on physalaemin action. It is concluded that physalaemin effect on SCC in frog skin is mediated by its interaction with NK1 receptors.
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PMID:Action of physalaemin on the ionic transport across the frog skin. 971 52

This study analyses the anti-hyperalgesic properties of the hydroalcoholic extract (HE) and the sesquiterpene polygodial isolated from the barks of Drymis winteri (Winteraceae). The HE (10 to 60 mg kg(-1), i.p. or 100 to 600 mg kg(-1), p.o.), 4 h prior, produced significant inhibition of abdominal constrictions caused by i.p. injection of acetic acid, kaolin and zymosan in mice. The mean ID50s were: 21.4, 33.7 and 36.6 mg kg(-1); 173.0, 123.0 and 366.0 mg kg(-1), by i.p. and by oral route, respectively. This effect lasted for up to 8 h. The HE at the same range of doses produced dose-related inhibition of both phases of the formalin-induced licking. The calculated mean ID50s values for the early phase were: 26.1 and 43.0 mg kg(-1), while for the late phase they were 7.3 and 72.7 mg kg(-1), respectively, when given by i.p. and by oral route. The HE (10 to 60 mg kg(-1), i.p. or 25 to 200 mg kg(-1), p.o.), 4 h prior, produced significant inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 18.0 and 68.0 mg kg(-1), respectively. The HE (3 to 100 mg kg(-1), p.o., 1 h) inhibited in a graded manner, the hyperalgesia induced by bradykinin (3 nmol/paw) or substance P (10 nmol/paw) in rat paw, with mean ED50 values of 54.5 and 53.7 mg kg(-1), respectively. However, the HE did not affect the hyperalgesia induced by carrageenan or PGE2. When assessed in the hot-plate test, the HE (200 mg kg(-1), p.o.) was inactive. Naloxone (1 mg kg(-1), i.p.) significantly reversed the antinociceptive effects caused by either morphine (5 mg kg(-1), s.c.) or by HE (60 mg kg(-1), i.p.). Polygodial (0.1 to 10 mg kg(-1), i.p.) produced significant inhibition of acetic acid, kaolin and zymosan-induced writhing in mice, being about 14 to 27-fold more potent than the HE at the ID50 level. Together these data provide support for a long-lasting anti-hyperalgesic property for the active principle(s) present in the barks of D. winteri when assessed in several models of inflammatory or neurogenic pain. Its actions involve, at least in part, an interaction with opioid pathway through a naloxone-sensitive mechanism, seeming not to be related with a non-specific peripheral or central depressant actions. Finally, the sesquiterpene polygodial isolated from this plant, appears to be mainly responsible for the anti-hyperalgesic properties of the extract.
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PMID:Anti-hyperalgesic properties of the extract and of the main sesquiterpene polygodial isolated from the barks of Drymis winteri (Winteraceae). 971 24

Release of substance P (SP) from sensory nerve endings of the tracheobronchial system modulates airway smooth muscle contraction and may cause relaxation of precontracted airways. We sought to elucidate the effect of postnatal maturation on SP-induced relaxation of precontracted airways and determine the roles of endogenously generated nitric oxide (NO) and prostaglandins (PGs). Cylindrical airway segments were isolated from the midtrachea of rats at four different ages, 1, 2, and 4 wk and 3 mo, and contracted to 50-75% of the maximum response induced by bethanechol. SP was then administered in the absence and presence of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the PG inhibitor indomethacin, or both. Relaxation of airways with SP decreased significantly with advancing postnatal age. SP-induced tracheal relaxation was consistently attenuated by pretreatment with L-NAME, indomethacin, or both. In a different group of animals, L-NAME significantly attenuated the relaxant response of airways to PGE2 exposure, but indomethacin had no significant effect on the relaxant response to exogenous NO. We conclude that SP induces a relaxant effect on precontracted airway smooth muscle, which decreases with advancing age and is mediated via SP-induced release of NO and/or PG.
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PMID:Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development. 988 55

The liberation of calcitonin gene-related peptide from rat skin in vitro induced by antidromic electrical stimulation of unmyelinated units is demonstrated. Prostaglandin E2 was released concomitantly during C-fiber stimulation. A dose-dependent increase in prostaglandin E2 content of the eluate was also observed in response to stimulation with substance P (10(-7) to 10(-5) M) and calcitonin gene-related peptide (10(-6) and 10(-5) M). In contrast, prostaglandin E2 did not induce measurable release of neuropeptides. The amount of calcitonin gene-related peptide released during suprathreshold electrical stimulation increased with pulse frequency. Calcitonin gene-related peptide and prostaglandin release were completely inhibited in the presence of EMD 61753, a selective kappa-opioid receptor agonist. No significant release of substance P was observed. The data demonstrate a primary release of calcitonin gene-related peptide from unmyelinated but not myelinated primary afferents in the rat skin, which is accompanied by a secondary liberation of prostaglandin E2, connecting neurogenic inflammation to general mechanisms of inflammation.
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PMID:Calcitonin gene-related peptide and prostaglandin E2 but not substance P release induced by antidromic nerve stimulation from rat skin in vitro. 1005 Dec 37

Neurogenic inflammation of the dura, expressed in plasma extravasation and vasodilatation, putatively contributes to different types of headache. A novel in vitro preparation of the fluid-filled skull cavities was developed to measure mediator release from dura mater encephali upon antidromic electrical stimulation of the trigeminal ganglion and after application of a mixture of inflammatory mediators (serotonin, histamine and bradykinin, 10(-5) M each, pH 6.1) to the arachnoid side of rat dura. The release of calcitonin gene-related peptide, substance P and prostaglandin E2 from dura mater was measured in 5-min samples of superfusates using enzyme immunoassays. Orthodromic chemical and antidromic electrical stimulation of dural afferents caused significant release of calcitonin gene-related peptide (2.8- and 4.5-fold of baseline). The neuropeptide was found to be increased during the 5-min stimulation period and returned to baseline (20.9 +/- 12 pg/ml) in the sampling period after stimulation. In contrast, release of substance P remained at baseline levels (19.3 +/- 11 pg/ml) throughout the experiment. Prostaglandin E2 release was elevated during chemical and significantly also after antidromic electrical stimulation (6- and 4.2-fold of baseline, which was 305 +/- 250 pg/ml). Prostaglandin E2 release outlasted the stimulation period for at least another 5 min. The data support the hypothesis of neurogenic inflammation being involved in headaches and provide new evidence for prostaglandin E2 possibly facilitating meningeal nociceptor excitation and, hence, pain.
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PMID:Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro. 1019 23

1. Spinal prostanoids are implicated in the development of thermal hyperalgesia after peripheral injury, but the specific prostanoid species that are involved are presently unknown. The current study used an in vitro spinal superfusion model to investigate the effect of substance P (SP), N-methyl-d-aspartate (NMDA), and capsaicin on multiple prostanoid release from dorsal spinal cord of naive rats as well as rats that underwent peripheral injury and inflammation (knee joint kaolin/carrageenan). 2. In naive rat spinal cords, PGE2 and 6-keto-PGF1alpha, but not TxB2, levels were increased after inclusion of SP, NMDA, or capsaicin in the perfusion medium. 3. Basal PGE2 levels from spinal cords of animals that underwent 5-72 h of peripheral inflammation were elevated relative to age-matched naive cohorts. The time course of this increase in basal PGE2 levels coincided with peripheral inflammation, as assessed by knee joint circumference. Basal 6-keto-PGF1alpha levels were not elevated after injury. 4. From this inflammation-evoked increase in basal PGE2 levels, SP and capsaicin significantly increased spinal PGE2 release in a dose-dependent fashion. Capsaicin-evoked increases were blocked dose-dependently by inclusion of S(+) ibuprofen in the capsaicin-containing perfusate. 5. These data suggest a role for spinal PGE2 and NK-1 receptor activation in the development of hyperalgesia after injury and demonstrate that this relationship is upregulated in response to peripheral tissue injury and inflammation.
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PMID:In vitro prostanoid release from spinal cord following peripheral inflammation: effects of substance P, NMDA and capsaicin. 1021 26

Activation of renal pelvic sensory nerves by increased pelvic pressure results in a renal pelvic release of substance P that is dependent on intact prostaglandin synthesis. An isolated renal pelvic wall preparation was used to examine whether PGE2 increases the release of substance P from renal pelvic sensory nerves and by what mechanisms. The validity of the model was tested by examining whether 50 mM KCl increased substance P release from the pelvic wall. Fifty millimolar KCl produced an increase in substance P release, from 9.6 +/- 1.6 to 26.8 +/- 4.0 pg/min, P < 0.01, that was blocked by the L-type calcium blocker verapamil (10 microM). PGE2 (0.14 microM) increased the release of substance P from the pelvic wall from 8.9 +/- 0.9 to 20.6 +/- 3.3 pg/min, P < 0.01. PGE2 failed to increase substance P release in a calcium-free medium. The PGE2-induced substance P release was blocked by the N-type calcium blocker omega-conotoxin (0.1 microM) but was unaffected by verapamil. In conclusion, PGE2 increases the release of substance P from renal pelvic sensory nerves by a calcium-dependent mechanism that requires influx of calcium via N-type calcium channels.
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PMID:PGE2 increases substance P release from renal pelvic sensory nerves via activation of N-type calcium channels. 1023 13

Substance P (SP) induces increased vascular permeability, vasodilatation and granulocyte infiltration upon intradermal injection. Studies with antagonists and mast cell-deficient mice have suggested that granulocyte infiltration in response SP is mediated by leukotriene (LT) B4 derived from mast cells. However, the release of LTB4 has not been detected using mast cells isolated from human skin. Here we report the release of LTB4, prostaglandin (PG) D2 and histamine from guinea pig skin tissue in response to SP. The release of these agents occurred in a dose-dependent manner over a concentration range of SP from 1 x 10(-6) to 3 x 10(-4) M. No detectable PGE2 was released at any concentration up to 3 x 10(-4) M SP. The kinetics of histamine release induced in response to SP was more rapid than that induced by antigen. By comparison, SP-induced and antigen-induced release of LTB4 and PGD2 were similar, but slower than the histamine release. In the absence of extracellular Ca2+, release of histamine and PGD2 in response to SP was partially impaired, but to a lesser extent than that induced by antigen. On the other hand, LTB4 release in response to both SP and antigen was abolished under the same conditions. These results indicate that SP induces the release of LTB4, as well as histamine and PGD2, in the skin most likely from mast cells by a mechanism which may be different from that of mediator release in response to antigen.
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PMID:Substance P- and antigen-induced release of leukotriene B4, prostaglandin D2 and histamine from guinea pig skin by different mechanisms in vitro. 1048 19

In isolated strips of the hamster urinary bladder the selective tachykinin NK2 receptor agonist [betaAla8]NKA(4-10) induced a concentration-dependent (1 nM-10 microM) contraction (EC50 104 nM) associated with significant release of prostaglandin E2 (PGE2, 50+/-17 pg/mg tissue). In mucosa-free bladder strips [betaAla8]NKA(4-10) was as potent as in the presence of mucosa (EC50 46 nM), although the evoked PGE2 release was significantly less than in controls (6+/-1.7 pg/mg tissue). Dexketoprofen (10 microM) produced a significant but limited rightward shift of the concentration/response curve to [betaAla8]NKA(4-10) both in the presence and absence of the mucosal layer: the EC50 for [betaAla8]NKA(4-10) was increased five- and threefold, respectively. The evoked PGE2 release was abolished in both cases. The selective tachykinin NK2 receptor antagonist, nepadutant (10 nM-1 microM) produced a concentration-dependent and even inhibition of both contraction and PGE2 release induced by [betaAla8]NKA(4-10). The L-type calcium channel blocker, nifedipine (1 microM) and the non-selective cationic channel blocker SKF 96365 (30 microM) both inhibited the contractile response to [betaAla8]NKA(4-10) (89+/-2 and 83+/-2% inhibition, respectively). The evoked PGE2 release was not affected by nifedipine but was almost abolished by SKF 96365. Arachidonic acid (100 microM) induced a contractile response (5.9+/-0.7 mN) associated with a large production of PGE2 (383+/-78 pg/mg tissue). The contractile response to arachidonic acid was inhibited by both nifedipine (1 microM) and SKF 96365 (30 microM) (83+/-5 and 79+/-3% inhibition, respectively). The PGE2 production induced by arachidonic acid was markedly inhibited by SKF 96365 only (about 94% inhibition). Exogenous PGE2 contracted hamster bladder strips in the presence of dexketoprofen (EC50 1 microM) and strongly potentiated the contractile response to a submaximal concentration of [betaAla8]NKA(4-10). In anaesthetized hamsters the administration of [betaAla8]NKA(4-10) (10 nmol/kg, i.v.) produced a contractile response of the urinary bladder (13+/-0.4 mmHg) that was inhibited partly by dexketoprofen (25+/-3 and 35+/-4% inhibition for 0.2 and 2 mg/kg, i.v. dexketoprofen, respectively). We conclude that activation of tachykinin NK2 receptors determines prostanoid synthesis/release in the hamster urinary bladder and that this effect is largely ascribable to structures present in the bladder mucosa. Prostanoids generated following NK2 receptor activation amplify the direct contractile effect of NK2 receptor agonists. This latter response is largely due to activation of L-type calcium channels (nifedipine-sensitive) although this source of calcium apparently is not essential for activation of prostanoid synthesis.
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PMID:Role of prostanoids in the contraction induced by a tachykinin NK2 receptor agonist in the hamster urinary bladder. 1076 62

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