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)

An isolated spinal cord-tail preparation of the newborn rat was developed and used for studying the effects of various drugs. The cord and the tail were separately perfused with oxygenated artificial cerebrospinal fluid. Application of capsaicin in a small amount to the tail induced a depolarizing response of the lumbar ventral root (L3-L5) lasting for about 30 sec. The stimulating action of capsaicin was potentiated by previous perfusion of the tail with a medium containing prostaglandin E1 or E2. The capsaicin-induced nociceptive reflex was depressed by application to the spinal cord of morphine, Met-enkephalin, dynorphin (1-13), somatostatin, adenosine, GABA and a substance P (SP) antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP, and potentiated by bicuculline. The present preparation will be useful for the future studies on pain and analgesic drugs.
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PMID:Effect of a substance P antagonist on capsaicin-induced nociceptive reflex in the isolated spinal cord-tail preparation of the rat. 244 68

1 Acetylcholine, substance P, prostaglandin E1 and the nitrovasodilator glyceryl trinitrate induced concentration-dependent relaxations of endothelium-intact strips of rabbit coeliac artery precontracted with noradrenaline. 2 Endothelium-denuded strip preparations contracted to acetylcholine and showed no response to substance P. The relaxant response to prostaglandin E1 was unimpaired after removal of endothelium, whereas the response to glyceryl trinitrate was increased. 3 A 20 min exposure of endothelium-intact strips to gossypol, an irreversible inhibitor of the production and/or release of endothelium-derived relaxing factor, abolished vasodilatation in response to the endothelium-dependent agents acetylcholine and substance P, did not change relaxations to prostaglandin E1, but significantly enhanced relaxations in response to glyceryl trinitrate. 4 In view of the assumed common mechanism of action of endothelium-derived relaxing factor and nitrovasodilators, these results suggest an interference of the two active principles at the level of the vascular smooth muscle cell.
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PMID:Selective inhibition by gossypol of endothelium-dependent relaxations augments relaxations to glyceryl trinitrate in rabbit coeliac artery. 244

Vasodilation mediated by endothelium-derived relaxing factor (EDRF) has been demonstrated in large conduit arteries in vitro. In the present study we investigated whether the EDRF mechanism is also present in resistance arteries of a peripheral vascular bed, namely the hindlimb of the rabbit. The right femoral artery of anesthetized rabbits was cannulated and blood was supplied through a shunt from the carotid artery. Femoral arterial blood flow and pressure were measured in the shunt. Systemic pressure was measured in the abdominal aorta. The hemodynamic effects of endothelium-dependent and -independent vasodilators (infused into the shunt) were measured before and after treatment of the vascular bed with gossypol or p-bromophenacyl bromide (p-BPB). Gossypol, a polyphenolic antioxidant, is a selective and irreversible inhibitor of the EDRF-mediated vasodilation in isolated arteries; p-BPB is an alkylating agent and also produces irreversible inhibition of endothelium-mediated relaxations in vitro. During inhibitor treatment the hindlimb was temporarily isolated from the blood circulation and perfused with a cell-free medium; the venous effluent was drained off so that only minimal amounts of inhibitor reached the systemic circulation. The endothelium-dependent vasodilators acetylcholine (ACh) and substance P, and the endothelium-independent vasodilators prostaglandin E1 (PGE1) and glyceryl trinitrate (GTN) induced concentration-dependent increases in femoral arterial flow (and decreases in vascular resistance). Gossypol treatment had no direct effect on systemic blood pressure or femoral arterial flow. However, after gossypol, the effects of ACh and substance P on vascular resistance were almost abolished, but there was no significant effect on the responses to PGE1 and GTN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-derived relaxing factor is likely to modulate the tone of resistance arteries in rabbit hindlimb in vivo. 244 63

The in vivo blood pressure lowering effect of three vasodilators whose in vitro effects are endothelium-dependent (acetylcholine, substance P and adenosine triphosphate) was reduced by 40-60% after systemic treatment of the animals with gossypol. In vitro, gossypol is an inhibitor of the production and/or release of endothelium-derived relaxing factor. Systemically administered gossypol had no effect on blood pressure decreases produced by the endothelium-independent agents prostaglandin E1 (alprostadil) and glyceryl trinitrate. These results suggest that endothelium-mediated vasodilator mechanisms could participate in blood pressure regulation.
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PMID:Gossypol attenuates selectively the blood pressure lowering effect of endothelium-dependent vasodilators in the rabbit in vivo. 245 Jul 61

When rats were pretreated by intraplantar or i.v. injection of various inflammatory mediators, the vasopressor effect of i.a. norepinephrine in the subsequently isolated perfused hindlegs of the rats was found to be partly depressed. This vasodepression could also be detected if mediators were directly co-perfused in the isolated hindlegs. The vasodepressor effect was strongest following histamine pretreatment and co-perfusion, respectively, whereas endotoxin 0111:B4, PAF-acether, PGE1, and LTD4 were less effective. Only weak or no vasodepression could be induced by bradykinin, serotonin, lysolecithin, and substance P (1-11). The significance of the results is discussed with respect to anaphylactic disorders.
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PMID:Vasodepression ex vivo after administration of inflammatory mediators in vivo in the rat. 247 18

A blister model of inflammation in the rat hind footpad was used to study the possible interaction between noradrenergic sympathetic fibres and primary afferent unmyelinated fibres which contain substance P (SP), the putative mediator of neurogenic inflammation. Plasma protein extravasation (PE) was used as a measure of the response of post-capillary venules to SP perfused over the blister base. In rats treated with 6-hydroxydopamine (6-OHDA, 75 mg/kg/day for 3 days intraperitoneally) PE was reduced by 42%. However, in rats treated by local perfusion of the blister base with noradrenaline (1 mumol/L) PE was also reduced. As prostaglandins have been postulated to effect some sympathetically mediated responses, PGE1 (1 mumol/L) was perfused over the blister base and found to enhance the response to SP. The results indicate that sympathetic noradrenergic neurones may contribute to SP-induced plasma extravasation by a sensitising mechanism independent of noradrenaline.
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PMID:Sympathetic neurons modulate plasma extravasation in the rat through a non-adrenergic mechanism. 248 53

Vasodilation mediated by endothelium-derived relaxing factor (EDRF) has been demonstrated in large conduit arteries in vitro. Experiments were undertaken to investigate whether EDRF can also be produced in the microcirculation and thus could participate in the regulation of peripheral resistance. In a first series of experiments we studied a peripheral vascular bed, the hindlimb of the rabbit. The right femoral artery of anaesthetized rabbits was cannulated and blood was supplied through a shunt from the carotid artery. Blood flow through the hindlimb was measured in the shunt. Systemic pressure was measured in the abdominal aorta. Vascular resistance in the hindlimb was calculated from the two parameters. The haemodynamic effects of endothelium-dependent and -independent vasodilators (infused into the shunt) were measured before and after selective treatment of the vascular bed with gossypol, an irreversible inhibitor of the production or release of EDRF. The endothelium-dependent vasodilators acetylcholine and substance P, and the endothelium-independent vasodilators prostaglandin E1 and glyceryl trinitrate induced dose-dependent decreases in vascular resistance. Gossypol almost abolished the effects of acetylcholine and substance P on vascular resistance, but had no significant effect on the responses to prostaglandin E1 and glyceryl trinitrate. Also the decrease in peripheral resistance produced by hydralazine was not affected by gossypol although in the same rabbits the response to acetylcholine was inhibited by more than 70%. In bioassay experiments the production of EDRF was measured from cultured human microvascular (omentum) and macrovascular (umbilical vein) endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Formation and functional importance of endothelium-derived relaxing factor (EDRF) and prostaglandins in the microcirculation. 251 74

Effects of the peptidoleukotriene receptor antagonist, SK&F 104353, were examined in vitro using stripped rat ileal mucosa in Ussing chambers. Changes in short-circuit current (Isc), transepithelial conductance (G1) and unidirectional and net Na+ and Cl fluxes measured in the absence or presence of SK&F 104353 (1 microM) revealed that serosal addition produced a decrease in net Na+ absorption and serosal-to-mucosal Cl- flux. Serosal addition of leukotriene (LT)D4 (10 muM) or LTE4 (10 microM) elicited transient increases in Isc and sustained decreases in G1 which were antagonized by serosal addition of SK&F 104353 in a concentration-dependent manner. Mucosal addition of SK&F 104353 (1 microM) also reduced the increase in Isc elicited by LTD4 (10 microM). LTD4 (10 microM) decreased unidirectional and net Na+ and Cl- fluxes along with G1 in the steady state. All of these changes were abolished by pretreatment with SK&F 104353 (1 microM). The intestinal secretagogues prostaglandin F2 alpha, histamine, serotonin, substance P and the thromboxane mimic, U46619, produced changes in Isc qualitatively similar to those of LTD4. However, the transient increase in Isc produced by these secretagogues was not antagonized by SK&F 104353 (1 microM). Additionally, lysbradykinin- and prostaglandin E1-induced increases in Isc were not antagonized by SK&F 104353 (1 microM). Stimulation with histamine (10 microM) or pretreatment with LTB4 (5 microM) did not alter the increase in Isc or decrease in Gt produced by the subsequent addition of LTD4 (10 microM). Pretreatment of the tissues with mepyramine (10 microM) also did not reduce the increase in Isc elicited by LTD4 (10 microM), although it inhibited completely the increase in Isc produced by histamine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:SK&F 104353: selective antagonism of peptidoleukotrine-induced changes in electrolyte transport by rat ileal mucosa in vitro. 255 22

The relationship between glucose metabolism and cyclic-AMP production in dental pulp in the presence of chemical mediators was investigated in vitro. It is generally accepted that oxidation of glucose-6-14C is indicative of metabolism by the glycolytic pathway whereas that of glucose-1-14C occurs by the hexose monophosphate shunt. The 14CO2 productions from both routes were compared in dental pulp from cattle and rats in the presence of each of several chemical mediators: bradykinin (1.7-3.3 micrograms/ml), prostaglandin E1 (0.3 micrograms/ml), prostaglandin E2 (0.3 micrograms/ml), histamine (33 micrograms/ml), and 5-hydroxytryptamine (33 micrograms/ml). The effects of dental filling materials on glucose oxidation, and cyclic-AMP production by chemical mediators in pulp tissues were also investigated. The results obtained were as follows: 1) Glucose oxidation in dental pulp was stimulated by chemical mediators generally by way of the Embden-Meyerhof Parnas pathway, and was further stimulated by the medium containing bradykinin. However, it was depressed in the presence of higher concentrations of chemical mediators, especially depressed in the HMS pathway. 2) The oxidation ratio of glucose-1-14C to glucose-6-14C (G1/G6) in dental pulp was 4 to 8 in the cattle and 0.6 in the rat, showing clear differences in glucose oxidation between the two animals. 3) Moreover, glucose oxidation in rat dental pulp was 60 to 80 times higher in the EMP pathway and 5 to 10 times higher in the HMS pathway than those in the cattle. 4) Dental filling materials such as silicate cement, zinc phosphate cement, calcium hydroxide, and eugenol cement severely depressed glucose-6-14C oxidation in bovine dental pulp when used at high concentrations, but not at low concentrations. 5) The chemical mediators tested in this experiment (PGE1, PGE2, histamine, 5-HT, bradykinin, and substance P) stimulated cyclic AMP production in rat dental pulp. The production was highest with PGE1 and PGE2. The cyclic AMP production was further stimulated by addition of histamine or 5-HT to the medium containing PGE1 or PGE2.
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PMID:[Studies on the relation between glucose metabolism and c-AMP formation in dental pulps in the presence of inflammatory chemical mediators in vitro]. 256 77

1. A simple desensitization protocol was set up using capsaicin and isolated, spontaneously beating atria of guinea-pigs to assess the possible participation of cardiac, capsaicin-sensitive, substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing sensory nerve fibres, in the cardiac stimulatory effects of bradykinin (Bk), kallidin (Kd), 5-hydroxytryptamine (5-HT), histamine, prostaglandin E2 (PGE2), prostaglandin E1 (PGE1), prostaglandin F2 alpha, (PGF2 alpha), adrenaline (Ad), glucagon, nicotine and angiotensin II (AII). 2. The positive chronotropic and inotropic effects of Bk, Kd and 5-HT were markedly reduced in capsaicin-desensitized atria compared to control. The percentage inhibition of the chronotropic and inotropic responses to the three agonists seemed to be inversely related to the concentration of agonist used and to vary also with the type of cardiac effect produced by the drug (for Bk the percentage inhibition was: 36-81% (chronotropic effect) and 62-86% (inotropic effect); for Kd: 61-78% (chronotropic effect) and 53-77% (inotropic effect); for 5-HT: 25-66% (chronotropic effect) and 40-64% (inotropic effect]. 3. The positive chronotropic and inotropic effects of histamine, PGE1, PGE2, PGF2 alpha, glucagon and AII had similar amplitudes in capsaicin-desensitized and control atria. 4. The positive chronotropic and inotropic effects of Ad and nicotine were differentially affected by capsaicin desensitization. The inotropic effects of 7.5 x 10(-7) and 7.5 x 10(-6) M Ad were reduced by 41 and 27% respectively, in capsaicin-desensitized atria compared to control. The chronotropic effects of 1.54 x 10(-5) and 6.17 x 10(-5) M nicotine were inhibited by 57 and 26% respectively, by capsaicin desensitization. On the other hand, the chronotropic effect of Ad and the inotropic action of nicotine were of similar amplitude in capsaicin-desensitized and control atria. 5. These results were taken as an indication that a substantial part of the chronotropic and inotropic effects of Bk, Kd or 5-HT in guinea-pig atria, unlike those of histamine, PGE1, PGE2 PGF2 alpha, glucagon and AII, might be the result of stimulation of capsaicin-sensitive, SP- and CGRP- containing sensory nerve fibres. The slight, differential inhibition of the chronotropic and inotropic effects of Ad and nicotine by capsaicin desensitization suggests a minor contribution by cardiac, capsaicin-sensitive sensory nerve fibres to the effects of nicotine and Ad in guinea-pig atria.
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PMID:Effects of capsaicin desensitization on the stimulatory effect of kinins, prostaglandins, biogenic amines and various drugs in guinea-pig isolated atria. 272 Feb 92


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