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)

Recent reports have shown that cultured endothelial cells release into the culture medium a substance (or substances) that contracts isolated preparations of arterial smooth muscle [endothelial-derived constrictor factor (EDCF)]. To evaluate the coronary and cardiac effects of EDCF, isolated rabbit hearts retroperfused in a nonrecirculating system with Krebs-Henseleit solution were challenged with bolus injections (100-600 microliter) of either serum-free minimum essential medium (vehicle) or aortic endothelial cell supernates concentrated in minimum essential medium (EDCF). EDCF, but not its vehicle, produced dose-dependent coronary vasoconstriction unaccompanied by changes in left ventricular contraction or heart rate. The constrictor responses were remarkably well sustained with little or no decrement in resistance occurring over a 15-min observation period. Nitroprusside inhibited the development of and reversed on-going vasoconstriction evoked by EDCF. Neither meclofenamate nor diethylcarbamazine influenced EDCF-induced pressor responses, thereby negating a role for arachidonic acid metabolites. Coronary vasoconstriction induced by EDCF also was unaffected by blockade of alpha-adrenergic, histaminergic or serotonergic receptors. Incubation of EDCF with trypsin attenuated the pressor effects markedly, suggesting that EDCF may be a peptide. Roles for angiotensin or substance P were ruled out, however, as saralasin failed to influence EDCF-induced constriction and since substance P was inactive in the perfused rabbit heart preparation. We conclude that a substance (or substances), probably a peptide, released from cultured endothelial cells provokes sustained coronary vasoconstriction by an unknown mechanism.
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PMID:Sustained coronary vasoconstriction provoked by a peptidergic substance released from endothelial cells in culture. 241 94

Endogenous nitric oxide (NO, endothelium-derived relaxing factor) was stimulatory for histamine- and suppressive for serotonin-induced paw edema of mice. This action was mediated by guanosine 3',5'-cyclic monophosphate production. Local injection of superoxide dismutase (SOD), catalase, NG-monomethyl-L-arginine (L-NMMA), methylene blue and Desferal (iron chelator) mixed with mediator suppressed histamine-induced edema at doses between 0.1 and 100 micrograms/kg and showed no or little stimulatory effect at higher doses. L-arginine reversed the effect of L-NMMA. Serotonin edema was enhanced by a high dose of these drugs. Their effect became suppressive as the histamine ratio was increased in edema induced by a histamine-serotonin mixture. This suggested that serotonin-induced vascular permeability decreased with a greater production of either O2- or NO. Cimetidine (H2-antagonist) was not effective in histamine edema of normal mice, but became suppressive (ED50 = 70 micrograms/kg) when 10 mg/kg L-NMMA was coinjected. SOD and methylene blue also rendered this edema sensitive to cimetidine. A simultaneous decrease in sensitivity to mepyramine (H1-antagonist) indicated that NO and oxyradicals kept H1-receptors activated. L-NMMA had no effect on bradykinin edema, but suppressed thrombin-, acetylcholine-, platelet-activating factor-, substance P- and FeCl3-induced paw edemata. Nitroprusside (NO donator) suppressed serotonin edema. N-Acetylcysteine and cytochrome c, but not ascorbate and hydroxyl radical scavengers suppressed histamine edema.
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PMID:Opposite effect of superoxide dismutase, L-arginine analogues, methylene blue and desferal: suppression of histamine-induced and stimulation of serotonin-induced paw edema in mice. 835 90

Substance P activation of neurokinin-1 (NK1) receptors on spinal sympathetic preganglionic neurons (SPN) influences blood pressure. We identified SPN likely to subserve the baroreceptor reflex and established if these neurons showed NK1 receptor-immunoreactivity. Nitroprusside (NP) infusion or inferior vena cava (IVC) constriction activated similar numbers of SPN. Of these, about 40% were NK1 receptor-immunoreactive after NP infusion, but only about 20% were NK1 receptor-immunoreactive after IVC constriction. The distribution of Fos/NK1 receptor SPN suggested that substance P may preferentially target sympathoadrenal SPN.
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PMID:Neurokinin-1 receptor immunoreactivity in hypotension sensitive sympathetic preganglionic neurons. 1159 14

The effects of acrolein exposure on tissue uptake and airway responses to substance P (SP) and nitroprusside (NIP) were determined in excised ferret tracheae exposed for 60 min to a constant flow of air or 0.3 and 3.5 ppm acrolein-air mixtures. Histological examination indicated that whereas the epithelium of an air-exposed trachea was intact with no apparent injury, acrolein-induced epithelium damage was more pronounced at 3.5 than at 0.3 ppm vapor concentration. The fractional uptake of acrolein into the tracheal tissue continually decreased during the 1 h of exposure and was found to be significantly concentration dependent at the 60 min measurement point. This suggests that the uptake process of acrolein in the mucosal layer is not linear and is dominated by irreversible reaction. In the absence of the neutral endopeptidase inhibitor, phosphoramidon, acrolein significantly increased the maximal response to SP. Pretreatment with phosphoramidon abolished the differential effect of acrolein on airway smooth muscle response to SP. Nitroprusside relaxed acrolein-exposed tracheal rings precontracted with carbachol to their baseline tone, but it induced relaxation of air-exposed tracheal rings below their initial resting tension, indicating the presence of endogenous as well as induced tone. Pretreatment with NIP also abolished the differential effect of acrolein on airway response to carbachol and modified the potency of this agonist. We conclude that acrolein-induced hyperresponsiveness of the underlying airway smooth muscle is linked to inactivation of neutral endopeptidase synthesis as well as to loss of epithelium-derived relaxation factor.
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PMID:Epithelium-linked smooth muscle hyperresponsiveness in ferret tracheae exposed to acrolein. 2178 1