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)

1. The release of PGs from the isolated perfused rabbit ear was measured by means of a radioimmunoassay. 2. Bradykinin in dose dependent amounts released mainly PGE (presumably PGE1) and in much smaller amounts also PGF. 3. Bradykinin released similar amounts of PGE in innervated and chronically denervated ears. 4. Indomethacin completely prevented the PGE release by bradykinin. 5. ACh showed a much lower efficacy than bradykinin in releasing PGE and PGF. Synthetic substance P was devoid of any PGE releasing action. 6. It is concluded that bradykinin increases its own algesic action by a concomitant rapid stimulation of the PGE synthesis, thus providing a mechanism for the facilitation of its own algesic action.
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PMID:Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. 100 30

Primary cultures of turbot (Scophthalmus maximus) brain astroglial cells established in medium containing fetal bovine serum contain increased proportions of 18:1(n-9), total (n-9) and (n-6) polyunsaturated fatty acids (PUFA) and greatly reduced (n-3) PUFA in comparison with turbot brain. Supplementation with a mixture of 5 microM eicosapentaenoic [20:5(n-3)] and 25 microM docosahexaenoic [22:6(n-3)] acids for 4 days significantly increased the percentages of these acids in total cellular lipid of turbot astrocytes and restored the (n-3) PUFA composition of the cells to that found in turbot brain. The production of prostaglandins (PG) E and F of the 2- and 3-series and leukotrienes (LT) C4 and C5 in response to various agonists was determined in PUFA-supplemented astrocytes. Calcium ionophore A23187, platelet activating factor and substance P stimulated the production of both PGF and PGE. Interleukin-1 beta significantly stimulated the production of PGF only. There were differences between the agonists in their effects on the relative levels of 2- and 3-series PGs produced. Only very low amounts of LTC were produced by the turbot astrocytes, with only substance P showing a minor stimulatory effect.
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PMID:Production of eicosanoids derived from 20:4n-6 and 20:5n-3 in primary cultures of turbot (Scophthalmus maximus) brain astrocytes in response to platelet activating factor, substance P and interleukin-1 beta. 893 2

In the present study, we examined whether substance P (SP) and SP methyl ester (SPME), a selective NK(1) agonist, cause biphasic responses consisting of endothelium-dependent relaxation (EDR) and contraction (EDC) in precontracted rabbit intrapulmonary arteries. In arteries contracted with PGF(2alpha) (2x10(-6) M), SP as well as SPME caused only EDR at low concentration (10(-9) M) and EDR followed by EDC at higher concentrations, indicating the involvement of NK(1) receptors. The SP (10(-8) M)-induced EDR was abolished in arteries moderately contracted by PGF(2alpha) (5x10(-7) M) and the EDC in arteries maximally contracted by PGF(2alpha) (10(-5) M), indicating that EDR and EDC are inversely dependent on preexisting tone. Indomethacin (10(-8) - 10(-6) M), a cyclo-oxygenase inhibitor, and ozagrel (10(-8) - 10(-6) M), a TXA(2) synthetase inhibitor attenuated the EDC in the SPME (10(-7) M)-induced biphasic response and markedly potentiated the EDR. AA-861 (10(-8) - 10(-6) M), a 5-lipoxygenase inhibitor, did not affect the EDR or EDC. L-N(G)-nitro-arginine methyl ester (10(-5) - 10(-4) M), a nitric oxide synthase inhibitor, attenuated the EDR and slightly potentiated the EDC. CP-99994 (10(-10) - 10(-8) M), an NK(1) antagonist, attenuated the EDC and potentiated the EDR in the SPME (10(-7) M)-induced biphasic response, while the NK(2) antagonist SR-48968 (10(-9) - 10(-7) M) had no effect. CP-99994 attenuated the SPME (10(-7) M)-induced EDC under EDR-blockade to a greater extent than the EDR under EDC-blockade, indicating that CP-99994 enhanced the EDR component by preferential inhibition of the EDC component. In conclusion, NK(1) agonists caused a biphasic endothelium-dependent response (EDR and EDC) in submaximally precontracted intrapulmonary arteries. The EDC and EDR mediated by NK(1) receptors may play physiological and/or pathophysiological roles in modulation of vascular tone.
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PMID:Endothelium-dependent relaxation followed by contraction mediated by NK(1) receptors in precontracted rabbit intrapulmonary arteries. 1069 93

Isoprostanes are a novel class of eicosanoids primarily formed by peroxidation of arachidonic acid. Because of their potential as inflammatory and/or hyperalgesic agents whose formation is largely independent of cyclooxygenases, we examined whether 8-iso prostaglandin E(2) (8-iso PGE(2)) or 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)) reduces mechanical and thermal withdrawal threshold in rats, and whether they sensitize rat sensory neurons. Injection of 1 microg of 8-iso PGE(2) (in 2.5 microl) into the hindpaw of rats significantly reduced mechanical and thermal withdrawal thresholds, whereas 1 microg of 8-iso PGF(2alpha) elicited a transient decrease in only the mechanical withdrawal threshold. Both isoprostanes enhanced the firing of C-nociceptors in a concentration-dependent manner when injected into peripheral receptive fields. Exposing sensory neurons grown in culture to 1 microM 8-iso PGE(2) or 8-iso PGF(2alpha) augmented the number of action potentials elicited by a ramp of depolarizing current. In contrast, 8-iso PGE(2) but not 8-iso PGF(2alpha) enhanced the release of substance P- and calcitonin gene-related peptide-like immunoreactivity from isolated sensory neurons. Ten micromolar 8-iso PGE(2) stimulated peptide release directly, whereas treatment with 1 microM 8-iso PGE(2) augmented the release evoked by either bradykinin or capsaicin. Pretreating neuronal cultures with the nonsteroidal anti-inflammatory drug ketorolac did not alter the sensitizing action of 8-iso PGE(2) on peptide release, suggesting that this action of the isoprostane was not secondary to the production of prostaglandins via the cyclooxygenase pathway. These data support the notion that isoprostanes are an important class of inflammatory mediators that augment nociception.
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PMID:Isoprostanes, novel eicosanoids that produce nociception and sensitize rat sensory neurons. 1086 92

The spinal cord is one of the sites where non-steroidal anti-inflammatory drugs (NSAIDs) act to produce analgesia and antinociception. Expression of cyclooxygenase(COX)-1 and COX-2 in the spinal cord and primary afferents suggests that NSAIDs act here by inhibiting the synthesis of prostaglandins (PGs). Basal release of PGD(2), PGE(2), PGF(2alpha) and PGI(2) occurs in the spinal cord and dorsal root ganglia. Prostaglandins then bind to G-protein-coupled receptors located in intrinsic spinal neurons (receptor types DP and EP2) and primary afferent neurons (EP1, EP3, EP4 and IP). Acute and chronic peripheral inflammation, interleukins and spinal cord injury increase the expression of COX-2 and release of PGE(2) and PGI(2). By activating the cAMP and protein kinase A pathway, PGs enhance tetrodotoxin-resistant sodium currents, inhibit voltage-dependent potassium currents and increase voltage-dependent calcium inflow in nociceptive afferents. This decreases firing threshold, increases firing rate and induces release of excitatory amino acids, substance P, calcitonin gene-related peptide (CGRP) and nitric oxide. Conversely, glutamate, substance P and CGRP increase PG release. Prostaglandins also facilitate membrane currents and release of substance P and CGRP induced by low pH, bradykinin and capsaicin. All this should enhance elicitation and synaptic transfer of pain signals in the spinal cord. Direct administration of PGs to the spinal cord causes hyperalgesia and allodynia, and some studies have shown an association between induction of COX-2, increased PG release and enhanced nociception. NSAIDs diminish both basal and enhanced PG release in the spinal cord. Correspondingly, spinal application of NSAIDs generally diminishes neuronal and behavioral responses to acute nociceptive stimulation, and always attenuates behavioral responses to persistent nociception. Spinal application of specific COX-2 inhibitors sometimes diminishes behavioral responses to persistent nociception.
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PMID:Prostaglandins and cyclooxygenases [correction of cycloxygenases] in the spinal cord. 1127 57

Several prostaglandin analogues used for glaucoma treatment cause increased pigmentation of the iris. The purpose of the present study was investigate whether latanoprost, a PGF(2 alpha) analogue, has any effect on the production of endogenous prostaglandins in iridial melanocytes, which could be important in the mechanism leading to increased pigmentation. Bovine and human iridial melanocytes in culture were used for the experiments. Production of endogenous prostaglandins was measured by enzyme immunoassay, and the melanin content was measured spectrophotometrically. In bovine iridial melanocytes, latanoprost acid caused a significant increase of the PGE(2) production, which could be blocked by indomethacin and NS398, indicating an involvement of cyclo-oxygenase 2. In order to study the selectivity of the phenomenon other endogenous substances/drugs were tested, e.g., acetylcholine, carbachol, noradrenaline, neuropeptide Y, substance P and alpha-MSH, but none was found to have any significant effect. Human iridial melanocytes also responded to latanoprost acid with increased production of PGE(2) and in 1 out of 5 individuals increased melanogenesis coincided with increased PGE(2) production. In bovine iridial melanocytes, latanoprost acid did not stimulate melanogenesis. These results indicate that latanoprost acid cause enhanced formation of endogenous prostaglandins that may have auto- and/or paracrine effects in the melanocytes, possibly associated with melanogenesis.
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PMID:Production of prostaglandin e(2) by iridial melanocytes exposed to latanoprost acid, a prostaglandin F(2 alpha) analogue. 1241 90

The effects of three vasoactive neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal polypeptide (VIP), on vasodilation and skin temperature were investigated in ovariectomized (OVX) and sham-operated control rats. CGRP (0.01-1 nmol), VIP (0.01-10 nmol) and SP (0.1-100 nmol) produced vasodilation in PGF(2 alpha) (10 microM)-induced contraction of mesenteric vascular beds isolated from OVX and sham-operated rats in a dose-dependent manner. Intravenous injection of CGRP (1-10 microg/kg), VIP (10-50 microg/kg) and SP (10-50 microg/kg) elevated the skin temperature in OVX and sham-operated rats in a dose-dependent manner. CGRP had the greatest effect on both parameters, followed by VIP, with the smallest effect in SP. These parallel increases of vasodilation and skin temperature with CGRP were significantly greater in OVX rats than in sham-operated rats. However, no significant differences were observed in VIP- or SP-induced vasodilation and skin temperature increases between OVX and sham-operated rats. These results suggest not only that CGRP is closely related to the elevation of skin temperature but also that CGRP-induced responses are more affected by ovarian hormone deficiency.
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PMID:Effects of the vasoactive neuropeptides calcitonin gene-related peptide, substance P and vasoactive intestinal polypeptide on skin temperature in ovariectomized rats. 1245 Jul 38

Placement of an ameroid constrictor in large-conduit pig coronary arteries causes progressive stenosis and distal myocardial ischemia. Blood perfusion in the ischemic region is partly dependent on vasomotor responses to neural and humoral factors distal to the occlusion site. To ascertain the degree of impairment of vascular function in pigs, the authors induced myocardial ischemia by placing an ameroid constrictor in the left circumflex coronary artery and examined vascular reactivity and histopathology distal to the constriction site. The sensitivity of the distal left circumflex coronary and nonoccluded control left anterior descending arteries to PGF(2alpha) was similar. After nitric oxide blockade using Nw-nitro-l-arginine methylester (l-NAME), the sensitivity and maximal contraction to PGF(2alpha) were significantly increased in both the left circumflex coronary (EC50: 5.86 +/- 0.74 vs. 3.28 +/- 0.84 microM; C(max): 4.63 +/- 0.28 vs. 6.25 +/- 0.30 g, P < 0.01) and left anterior descending (EC50: 6.57 +/- 0.73 vs. 2.78 +/- 0.16 microM; C(max): 5.09 +/- 0.37 vs. 6.95 +/- 0.39 g, P < 0.01) arteries. Substance P-induced relaxation (100 pM) was blocked to a larger degree in the distal left circumflex coronary artery when compared with the left anterior descending artery (76.9 +/- 4.2% vs. 56.4 +/- 3.1%, P < 0.05). Endothelium-independent relaxation to sodium nitroprusside was similar in the left circumflex coronary and left anterior descending arteries before and after nitric oxide blockade. Histopathologic examination showed no major differences between distal left circumflex coronary artery segments and left anterior descending artery controls. However, scanning electron microscopy showed endothelial hypertrophy and activation in specimens from the left circumflex coronary arteries. In summary, as a result of the major hemodynamic changes induced by a chronic constriction and eventual occlusion of a large coronary artery, distal segments underwent adaptive compensatory changes. Such compensation may be related to an increased nitric oxide production by the hypertrophic endothelium in response to alterations in coronary hemodynamics.
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PMID:Vasomotor function of pig coronary arteries after chronic coronary occlusion. 1265 62

Patients with acute pancreatitis often suffer from intestinal motility disturbances but the mechanism of this dysfunction is largely unknown. We studied the effect of acute necrotising pancreatitis (ANP) on in vivo gastrointestinal motility and in vitro intestinal contractility in mice. ANP was induced non-invasively by feeding young female mice a choline-deficient ethionine-supplemented (CDE) diet during 72 h. Gastric emptying and intestinal transit were measured in vivo 15 min after intragastric gavage of a semiliquid Evans blue bolus. Gastric and intestinal neuromuscular function was determined in vitro on isolated muscle strips. ANP significantly decreased gastric emptying from 61.2 +/- 9.8 to 34.9 +/- 7.1% and intestinal transit from 63.4 +/- 5.6 to 32.5 +/- 5.4%. ANP did not affect receptor-dependent and receptor-independent gastric muscle contractions except the contractions to substance P, which were slightly inhibited. In intestinal muscle strips, ANP significantly decreased contractions to EFS, carbachol, PGF(2alpha), substance P and KCl. Our results show that ANP delays gastric emptying in vivo, associated with a specific reduction in substance P contractility in vitro. ANP also impairs intestinal transit in vivo, associated with a non-specific reduction of intestinal contractility in vitro. We conclude that ANP impairs gastrointestinal motility in mice with underlying regional differences in the pathogenic mechanisms.
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PMID:Regional differences in gastrointestinal motility disturbances during acute necrotising pancreatitis. 1618 5

Maturational changes have been noted in neurally mediated contractile and relaxant responses in airways from New Zealand White rabbits. In this study, we focused on prostaglandins with bronchoprotective properties as potential modulators of airway tone in maturing rabbits. Tracheal rings from 1-, 2-, and 13-wk-old rabbits were assessed for neurally mediated contractile and relaxant responses produced by electrical field stimulation (EFS) of nerves in the presence and absence of the prostaglandin inhibitor, indomethacin (Indo). We also measured EFS-induced release of prostaglandin E(2) (PGE(2)) and the stable metabolite of prostacyclin, 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)). In the presence of Indo, EFS produced significant increases in contractile responses in segments from 1- and 2-wk-old animals but not in segments from 13-wk adult rabbits. Tracheal rings from 1- and 2-wk-old animals precontracted with neurokinin A (NKA) relaxed 100% in response to EFS when Indo was not in the bath. In rings from 13-wk-old animals, relaxation was 40%. With Indo, relaxation was abolished in 1-wk-old animals and reduced to 30% in the 2- and 13-wk-old groups. Buffer from baths collected after EFS had significant increases in PGE(2) and 6-keto-PGF(1alpha) released from tissues from 1- vs. 2- and 13-wk-old animals. Dose response curves to PGE(2) using tissues precontracted to NKA showed significant increases in relaxant responses in 1- and 2- vs. 13-wk-old rabbits. In rabbit airways, this study demonstrates enhanced modulation of airway tone by PGE(2) and greater release of the bronchoprotective prostaglandins PGE(2) and prostacyclin early in life.
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PMID:Modulation of airway responses by prostaglandins in young and fully grown rabbits. 1748 93


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