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)

Endothelial cells synthesize and metabolize vasoactive substances which are involved in the regulation of vascular tone. Among these factors, the endothelium-derived nitric oxide (NO) appears to be of major importance. Many studies observed an impairment of the generation, release, or the diffusion of endothelial NO across the vascular intima in laboratory animals with various experimental diseases such as hypercholesterolemia, atherosclerosis and hypertension. In human coronary arteries obtained from explanted hearts impaired endothelium-dependent relaxations were measured in atherosclerotic segments. The hypothesis of a decreased NO mediated vasodilation in patients with coronary artery disease was further underscored by in vivo studies in man using intracoronary infusions of the endothelium-dependent vasodilator acetylcholine and quantitative coronary angiographic measurements of the diameter changes. From these observations it was assumed that endothelial dysfunction, in particular a profound inability of the coronary endothelium to relax via NO dependent mechanisms may play an important role in the pathogenesis of abnormal coronary vasomotion. However, further investigations in man reveal that the ability of the coronary endothelium of patients with coronary artery disease or vasospastic angina to produce endothelial NO is less affected as judged from the effects of acetylcholine. In recent investigations a largely preserved endothelial function could be measured in these patients when the endothelium-dependent vasodilator substance P was used as a tool for the measurement of NO dependent relaxation. Thus, endothelial dysfunction does not appear to serve as a major cause of abnormal vasoconstriction in coronary artery disease or vasospastic angina in man.
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PMID:In vivo measurement of endothelium-dependent vasodilation with substance P in man. 128 20

The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret. 128 77

Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relaxations to SP in isolated rings of the pig carotid artery suspended in organ chambers for isometric tension recording. SP (10(-12)-10(-7) M) caused concentration-dependent relaxations of arteries precontracted with norepinephrine (10(-7) M). The relaxations were characterized by a partially transient relaxation (phase 1) and a sustained relaxation of the artery (phase 2). The inhibitor of nitric oxide formation, N omega-nitro-L-arginine (L-NNA) methyl ester caused a gradual increase in tension, the phase I response at 3 x 10(-10) to 3 x 10(-7) M SP was shifted to the right, but the maximal relaxation was comparable in the presence of L-NNA. However, the sustained relaxation after addition of substance P (phase II) was lost and tension in the presence of L-NNA returned to a level above that induced by L-NNA and norepinephrine (10(-9) M). These results suggest that the endothelium-dependent relaxations to SP, particularly the prolonged relaxation (phase II), are due to de novo synthesis of nitric oxide and hence fully abolished by a specific inhibitor.
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PMID:N omega-nitro-L-arginine blocks the second phase but not the first phase of the endothelium-dependent relaxations induced by substance P in isolated rings of pig carotid artery. 128 40

By using a simple platelet binding assay, we investigated whether endothelium-derived relaxing factor (EDRF) released from endocardial endothelium influences the adhesion of unstimulated platelets to these cells. Under basal conditions 8.0 +/- 0.32% of total platelets added adhered. The nitric oxide (NO) synthase inhibitor, i.e. NG-nitro L-arginine methyl ester (L-NAME), and the EDRF inhibitor haemoglobin (Hb) increased this adhesion, but another NO synthase inhibitor, NG-monomethyl L-arginine (L-NMMA), did not. The EDRF releasing agent substance P (SP) decreased adhesion, L-NMMA reversed this inhibition, whereas L-NAME and Hb did so only partially. Superoxide dismutase (SOD) caused a marked decrease in adhesion which was fully reversed by L-NMMA, L-NAME and Hb. SOD and SP together showed a cumulative effect on platelet adhesion; this inhibition was significantly reversed by all the EDRF inhibitors, although the levels of adhesion did not return to those seen under basal conditions. These results indicate that EDRF release can inhibit the adhesion of unstimulated platelets to cultured porcine endocardium and that NO synthase inhibitors have differential effects on basal and stimulated EDRF release by these cells.
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PMID:Endothelium-derived relaxing factor inhibits platelet adhesion to cultured porcine endocardial endothelium. 128 74

1. Endothelium-dependent relaxation is caused by an endothelium-derived relaxing factor (EDRF) identified as nitric oxide (NO). Our objective was to test whether one or several distinct endothelium-dependent relaxing factors exist. 2. In pig coronary arteries, a hyperpolarization accompanied by the relaxation caused by high concentrations of substance P (SP) and bradykinin (BK). 3. To examine the role played by nitric oxide and prostacyclin in the endothelium-dependent relaxations and hyperpolarizations caused by SP and BK on pig coronary arterial strips, the production of NO was inhibited by NG-nitro-L-arginine (L-NNA) and the production of prostacyclin was inhibited by indomethacin, while monitoring smooth muscle membrane potential and isometric tension. 4. Indomethacin had no effect on resting isometric tension nor on SP and BK relaxations of strips precontracted by prostaglandin F2 alpha. 5. L-NNA contracted arterial strips with intact endothelium, without changing the membrane potential of smooth muscles. 6. The inhibitor shifted to the right the concentration-response curve of kinins by 0.2 nM SP and 20 nM BK. It inhibited the maximal relaxations and hyperpolarizations by 30%. 7. The results show that, in pig coronary arteries, EDRF (NO) mainly controls the basal tension, whereas other factor(s) play(s) an important role in hyperpolarizations and relaxations caused by the kinins.
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PMID:Effect of nitro-L-arginine on endothelium-dependent hyperpolarizations and relaxations of pig coronary arteries. 128 11

Immunocytochemistry and a radioimmunoassay were used to investigate the existence and distributions of various regulatory peptide immunoreactivities (ir) in human submandibular and parotid glands. Numerous nerve fibers containing vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), or neuropeptide tyrosine (NPY) and C-flanking peptide of NPY (CPON)-ir were found in close proximity to acini, ducts and blood vessels. Only a few calcitonin gene-related peptide (CGRP)- and substance P (SP)-ir nerve fibers could be demonstrated and were mainly localized around blood vessels and ducts. Galanin and the recently discovered peptides helospectin and pituitary adenylate cyclase activating peptide were unable to be detected in the salivary glands studied. Preliminary quantitative investigations of four human submandibular glands using radioimmunoassay showed that VIP-ir had the highest concentration, followed by NPY-ir and CGRP-ir; SP-concentrations were below the detection limit. The possible physiological significance of these peptides for salivary secretion is discussed.
HNO 1992 Nov
PMID:[Peptidergic innervation of human salivary glands (parotid gland and submandibular gland)]. 133 45

Antropyloroduodenal motility was recorded in seven anesthetized dogs to assess the role of nitric oxide and L-arginine metabolites in nonadrenergic noncholinergic (NANC) mediation of pyloric relaxation. Pyloric activity induced by duodenal field stimulation was inhibited by antral field stimulation and electrical vagal stimulation. Intra-arterial NG-L-arginine-methyl-ester (L-NAME) reduced the inhibition from antral or vagal stimulation (P less than 0.05). Intravenous infusion of L-NAME also blocked the inhibitory effect of vagal and antral stimulation but left the tetrodotoxin-insensitive action of intra-arterial vasoactive intestinal peptide (VIP) and sodium nitroprusside unchanged. L-Arginine reversed the effect of L-NAME whereas D-arginine did not. L-NAME enhanced pyloric contractions to intra-arterial acetylcholine. The NANC inhibition of the substance P-stimulated pyloric response in vitro was blocked by L-NAME and reversed by addition of L-arginine. Sodium nitroprusside was effective as a relaxant in vitro but VIP was not. These data suggest that metabolites of L-arginine mediate neural inhibition of canine pyloric motor activity.
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PMID:Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo. 134 7

Neural control of the airways may be abnormal in asthma and neurogenic mechanisms may contribute to the pathophysiology of asthma. Cholinergic nerves are the predominant bronchoconstrictor pathway in airways and cholinergic neurotransmission may be increased in asthma by the effects of inflammatory mediators on afferent nerves (reflex effect) and on prejunctional receptors on postganglionic nerves. In addition there may be a defect in prejunctional M2-receptors on cholinergic nerves resulting in increased cholinergic neural effects. beta-Adrenoceptor function may be abnormal in asthmatic airways as a result of chronic inflammation, but alpha-receptors are probably unimportant in regulation of human airway tone. Inhibitory NANC nerves are the only bronchodilator pathway in human airways, and there is some evidence that the neurotransmitter is predominantly nitric oxide, although vasoactive intestinal peptide may be contributory. It is possible that i-NANC function may be abnormal in asthma as a consequence of inflammation. Unmyelinated sensory nerves contain a variety of potent inflammatory peptides, including substance P and neurokinin A, which might be released in chronic inflammation, particularly if there is a proliferation of these nerves, increased neuropeptide synthesis or reduced metabolism by neutral endopeptidase.
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PMID:Neural mechanisms in asthma. 135 67

Relaxation of penile corpus cavernosum smooth muscle is controlled by nerve and endothelium derived substances. In this study, endothelium-dependent relaxation of corporal smooth muscle was characterized and the role of arachidonic acid products of cyclooxygenase in endothelium-dependent relaxation was examined. Endothelium removal from rabbit corpora was performed by infusion with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate and was confirmed by transmission electron microscopy. Strips of human and rabbit corporal tissues were studied in the organ chambers for isometric tension measurement. The accumulation of cyclic guanosine monophosphate (cGMP) and the release of eicosanoids from corporal tissue was measured by radioimmunoassay and correlated to smooth muscle relaxation. Our study showed that relaxation of corpus cavernosum tissue to acetylcholine, bradykinin and substance P was endothelium-dependent; potentiated by indomethacin; and inhibited by NG-monomethyl-L-arginine, methylene blue or LY83583. Relaxation to papaverine and sodium nitroprusside was endothelium-independent, and unaffected by NG-monomethyl-L-arginine. Relaxation to vasoactive intestinal polypeptide was partially endothelium-dependent; potentiated by indomethacin; attenuated by NG-monomethyl-L-arginine or methylene blue. The tissue level of cGMP was enhanced by acetylcholine and nitric oxide. Methylene blue inhibited both basal and drug-stimulated levels of cGMP. The release of eicosanoids was enhanced by acetylcholine and blocked by indomethacin. In conclusion, nitric oxide or a closely related substance accounts for the activity of endothelium-derived relaxing factor in the corporal tissue. Inhibition of the release of eicosanoids potentiates the relaxing effect of nitric oxide. Nitric oxide increases tissue cGMP which appears to modulate corporal smooth muscle relaxation.
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PMID:Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone. 137 Mar 29

We and others have previously demonstrated that pretreatment with capsaicin produces an augmentation of vasoconstrictor responses to transmural nerve stimulation. In the present study, removal of endothelium by saponin or inhibition of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester produced an augmentation of vasoconstrictor responses to transmural nerve stimulation, responses which were further potentiated after treatment with capsaicin to desensitize sensory nerves. Capsaicin treatment decreased vasodilator responses to acetylcholine, but only at low acetylcholine concentrations. Potentiation by capsaicin of vasoconstrictor responses to transmural nerve stimulation was not affected by indomethacin. In the presence of guanethidine and methoxamine, transmural nerve stimulation caused vasodilator responses in the perfused rat mesentery. These responses were unaffected by removal of endothelium, as were vasodilator responses to exogenous calcitonin gene-related peptide (CGRP). In contrast, substance P did not produce any relaxation in the methoxamine-contracted mesentery. This study suggests that facilitation of vasoconstrictor responses to transmural nerve stimulation after capsaicin treatment primarily reflects inhibition of sensory nerve effects resulting in an increase of sympathetic vasoconstrictor actions. The present results also suggest that vasodilator responses to sensory nerve activation or exogenous CGRP are endothelium-independent and that substance P does not significantly contribute to modulation of vascular tone in the rat mesentery.
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PMID:Effect of endothelium on the actions of sympathetic and sensory nerves in the perfused rat mesentery. 137 71


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