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 (SP) is a potent endothelium-dependent vasodilator, and in porcine coronary arterioles the vasodilatory action of SP appears to be mediated entirely by nitric oxide. We tested the hypothesis that SP induces hyperpolarization in porcine coronary artery endothelial cells (PCAECs) by activating Ca(2+)-activated K+ (KCa) channels. With a bath Ca2+ concentration ([Ca2+]) of 1 mM, 10 nM SP elicited an increase in cytosolic [Ca2+] ([Ca2+]i) from a baseline of 25 +/- 4 nM to a peak of 808 +/- 120 nM, followed by a slowly declining plateau phase, which was absent in Ca(2+)-free bath and was abolished by addition of extracellular lanthanum or nickel. Whole cell current-clamp recordings revealed that the time course of SP-induced [Ca2+]i increases correlated closely with membrane hyperpolarization from an average resting potential of -42 +/- 2 to a peak of -79 +/- 2 mV. Under voltage clamp, SP stimulated whole cell currents with reversal potentials strongly dependent on extracellular K+ concentration. In 62% of patches tested, single-channel recordings revealed an intermediate-conductance K+ channel with activation highly correlated with the SP-induced [Ca2+]i increase. These results suggest that, in PCAECs, SP induces Ca2+ release from stores along with Ca2+ influx which activate a KCa channel leading to hyperpolarization. This may increase the driving force for Ca2+ entry and thus modulate endothelium-derived nitric oxide release.
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PMID:Mechanism of substance P-induced hyperpolarization of porcine coronary artery endothelial cells. 750 6

Within the human adrenal medulla immunoreactivity for the nitric oxide (NO)-generating enzyme nitric oxide synthase (NOS) was demonstrated in neurons, nerve fibres and chromaffin cells. Correlation of NOS-immunoreactivity with immunostaining for the peptides neuropeptide Y, somatostatin, substance P or vasoactive intestinal polypetide and for the catecholamine synthesis-enzyme tyrosine hydroxylase, respectively, in nerve cell bodies revealed colocalization of NOS only with substance P. Sparse intramedullary NOS-immunoreactive varicose nerve fibres associated with blood vessels or with chromaffin tissue were devoid of immunoreactivities for tyrosine hydroxylase or for the investigated peptides. Small NOS-immunolabeled cells belonged to the catecholamine-containing chromaffin cell population and costored VIP, but were distinct from the somatostatin- or neuropeptide Y- immunostained chromaffin subpopulations. The localization of NOS in distinct structural components of the human adrenal medulla indicates that NO is produced in different cell types and may reflect a differential role of this messenger system in autonomic control of adrenal gland function.
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PMID:Immunohistochemical demonstration of the synthesis enzyme for nitric oxide and of comediators in neurons and chromaffin cells of the human adrenal medulla. 750 10

The arrangement of the enteric nerve plexuses, and the distributions and projections of chemically specified neurons in the proximal colon of the guinea-pig were studied. The neural plexuses were examined using immunoreactivity to neuron specific enolase, and individual subpopulations were studied using antibodies raised against vasoactive intestinal peptide (VIP), substance P (SP), enkephalin, neuropeptide Y (NPY), gastrin releasing peptide (GRP), galanin, somatostatin, calbindin and calretinin. Nitric oxide producing neurons were studied using NADPH diaphorase histochemistry. The myenteric and submucous plexuses were not uniform around the entire circumference; at the mesenteric aspect of the colon there was almost no longitudinal muscle and the circular muscle was unusually thick and cord-like. In this region there was no tertiary plexus of fibres, and the ganglia of the myenteric and submucous plexuses were elongated in the direction of the circular muscle. Neuronal pathways within the antimesenteric aspect of the colon were investigated using nerve lesioning procedures. VIP, GRP, galanin, calbindin and NADPH diaphorase containing neurons lay in anally projecting pathways within the myenteric plexus, while enkephalin and somatostatin appeared in orally projecting nerve pathways. Few NPY immunoreactive nerve cells were found in the myenteric plexus of the proximal colon. The longitudinal muscle was innervated with VIP, SP, enkephalin and NADPH diaphorase containing fibres. The circular muscle was innervated by axons containing all substances investigated except NPY. Galanin, NPY, somatostatin and VIP fibres, all particularly dense in the mucosa, largely arose from nerve cell bodies in the submucous plexus. The results of the present study indicate that chemically specified neuronal populations in the proximal colon of the guinea-pig are more similar to the distal colon than the ileum, but that neuro-chemical and anatomical differences exist between the proximal and distal colon.
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PMID:Immunohistochemical analysis of neurons and their projections in the proximal colon of the guinea-pig. 751 May 7

Microglia (brain resident macrophages) have been found to be closely associated with beta amyloid containing plaques in brain tissue affected by Alzheimer disease (AD). To investigate whether beta amyloid peptide (beta AP) may activate microglia, the effects of synthetic beta AP (amino acids 1-40) and a subfragment (amino acids 25-35) on rat peritoneal macrophages were assessed using four different assays for activation. These peptides were compared with substance P, which has previously been shown to activate macrophages. Both beta amyloid peptides activated macrophages, as assessed by increased respiratory burst-associated oxygen consumption, by luminol-dependent chemiluminescence, and by aggregation. In addition, beta amyloid peptide (1-40) caused a significant increase in macrophage nitric oxide production, while subfragment (25-35) did not. Substance P caused significant activation as assessed by oxygen consumption and chemiluminescence, but not by aggregation or nitric oxide induction.
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PMID:Activation of macrophages by Alzheimer beta amyloid peptide. 751 Sep 64

Oxygen-derived free radicals, in particular superoxide anions, are known to inactivate the endogenous vasodilator endothelium-derived relaxing factor (EDRF) which is probably identical with the gaseous radical nitric oxide. It is possible that EDRF is not the target of superoxide anions but may also be an endogenous scavenger of this radical. Superoxide anions generated by the vessel wall were measured by a modified lucigenin-enhanced chemiluminescence technique in isolated pig coronary artery rings with intact endothelium. The addition of bovine superoxide dismutase, a scavenger of superoxide anions, decreased the chemiluminescence signal by 40 +/- 26% (mean +/- SD; P < 0.05; n = 21) indicating reduced generation/release of superoxide anions. In contrast, pretreatment of coronary artery rings with diethyldithiocarbamate, an inhibitor of the intrinsic copper-zinc superoxide dismutase, increased the chemiluminescence response by 136 +/- 128% (P < 0.05; n = 21). This increase in the chemiluminescence response induced by diethyldithiocarbamate-pretreatment was almost abolished in the presence of added bovine superoxide dismutase. Specific inhibition of the EDRF release with nitro-L-arginine (100 microM) did not affect the chemiluminescence response. On the other hand, stimulation of the EDRF release by substance P (10 nM) or addition of the endothelium-mediated relaxant bradykinin (0.1 microM) did not affect the chemiluminescence response. Stimulation of the EDRF release with serotonin (0.1 microM) significantly reduced the photon emission by 15 +/- 16% (n = 27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The basal and stimulated release of the endothelium-derived relaxing factor from isolated pig coronary arteries does not interfere with the vascular release of superoxide. 751 82

The hypothesis that the endothelium-derived relaxing factor/nitric oxide (EDNO) activity is elevated in chronic hypoxic pulmonary hypertension (CH-PHT) was tested using isolated Krebs-albumin-perfused rat lungs. Concentration of the EDNO decomposition products (NOx) in the lungs' effluent was measured by a modified chemiluminescence assay. The functional significance of basal EDNO production was studied by measuring the vasoconstrictor response to an EDNO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Reactivity to the endothelium-dependent vasodilator substance P and to exogenous NO was also studied. More NOx was found in effluent from CH-PHT (22.3 +/- 9.8 nM) than control (0.4 +/- 3.9 nM) lungs. The L-NAME-induced vasoconstriction was greater in CH-PHT than in control rats. The sensitivity, but not the maximal vasodilation, to exogenous NO was elevated in CH-PHT. The substance P-induced vasodilation was potentiated in CH-PHT compared with control rats and blocked by L-NAME in both groups. We conclude that basal and agonist-stimulated pulmonary EDNO activity is enhanced in this model of CH-PHT. The EDNO synthesis may play a counterregulatory role in CH-PHT.
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PMID:Increased endothelium-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats. 751 87

The ultrastructural distribution and subcellular localization of nitric oxide synthase (NOS) immunoreactivity and its possible colocalization with vasoactive intestinal polypeptide (VIP) and substance P in the muscularis externa in canine ileum and colon were studied by using polyclonal antisera raised against VIP, substance P, and cerebellar NOS. Immunogold staining, with or without silver enhancement, was carried out directly on ultrathin sections using single and two-faced double immunogold methods. NOS immunoreactivity was observed in nerve profiles in myenteric plexus and circular muscle layer. Immunoreactivity was occasionally detected in smooth muscle cells and interstitial cells of Cajal. The double immunostaining revealed NOS and VIP in the same nerve varicosities but never in the same organelles. NOS was localized in electron-dense material of undetermined nature, whereas VIP was associated with large granular vesicles. Substance P and NOS were never found in the same nerves. These results indicate that NOS is present in the enteric nerves containing VIP but in different organelles and that nitric oxide release probably does not occur by an exocytotic mechanism.
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PMID:Ultrastructural localization of nitric oxide synthase in canine small intestine and colon. 751 56

To evaluate the significance of repeated denudation injury in progression of atherosclerosis, we performed a single and then a second balloon denudation on the rabbit carotid arteries. Morphological examinations and organ chamber experiments were performed, and the results were compared. On morphological examinations, reendothelialization was almost completed in 2 wk after redenudation, whereas it required 6 wk after a single denudation. Intimal thickening progressed after redenudation. Organ chamber experiments showed that contractile responses and endothelium-independent relaxation remained unchanged after redenudation. Endothelium-dependent relaxations to acetylcholine, ADP, and substance P decreased progressively by repeating denudation. These relaxation responses were inhibited by NG-nitro-L-arginine, hemoglobin, and methylene blue and were considered to be associated with the production and/or release of endothelium-derived relaxing factor-nitric oxide (EDRF-NO). The diffusion barrier mechanism for the decreased endothelium-dependent relaxations was ruled out using sandwich experiments. In conclusion, repeated endothelial denudation caused progression of intimal thickening and acceleration of endothelial regeneration, and repeated endothelial regeneration resulted in progressively less production and/or release of EDRF-NO.
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PMID:Repeated endothelial removal augments intimal thickening and attenuates EDRF release. 751 59

Prostaglandin F2 alpha contracts coronary arteries smooth muscles under conditions of extra cellular and intracellular calcium depletion. In these conditions, nitrogen-oxide-containing vasodilators or natural EDRF(s) released by the kinins, substance P and bradykinin, from the endothelium relax strips of pig coronary arteries. This indicates that nitric oxide not only needs to lower cytosolic free calcium to relaxes the smooth muscles, but in addition another mechanism, independent of cytosolic calcium changes, is necessary to fully relax strips contracted by Prostaglandin F2 alpha.
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PMID:A vascular smooth muscles nitric oxide relaxation by a mechanism distinct of calcium changes. 751 9

We investigated the role of nitric oxide (NO) in the mediation of nerve stimulation-induced vasodilation in skeletal muscle. Hindlimb blood flow and vascular resistance were measured in pentobarbital-anesthetized, paralyzed, and guanethidine-treated rabbits. Centrifugal electrical stimulation of the sciatic nerve bundle induced reproducible, frequency-, voltage-, and pulse duration-dependent decrements in vascular resistance. The tachykinin antagonist CP-96,345 (1 mg/kg intravenously, i.v.) attenuated the vasodilation induced by intraarterially (i.a.) administered substance P but not by adenosine. Furthermore, CP-96,345 attenuated the decrease in vascular resistance in response to nerve stimulation, from 22.9 +/- 3.2 to 4.5 +/- 4.1% of control resting resistance (p < 0.005), without affecting basal vascular resistance. An inhibitor of NO formation, N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.v.), increased vascular resistance from 6.1 +/- 0.5 to 9.1 +/- 1.2 resistance units (p < 0.05) and significantly attenuated the vascular response to i.a. administered substance P but not adenosine. Finally, nerve stimulation-induced reduction in vascular resistance was attenuated by L-NAME, from 22.6 +/- 2.7 to 7.0 +/- 1.0% of control (p < 0.001). These findings suggest that tachykinins and NO are involved in mediation of vasodilation in response to the present type of nerve stimulation. The data are consistent with the hypothesis that NO is produced subsequent to neural release of tachykinin-type transmitter(s).
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PMID:Neurogenic vasodilation in rabbit hindlimb mediated by tachykinins and nitric oxide. 751 11


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