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)

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

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

1. The effects of L-NG-nitroarginine (L-NOARG) and L-NG-nitroarginine methyl ester (L-NAME) on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig coronary bed, by use of a Langendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The vasodilator responses evoked by low doses of 5-HT (5 x 10(-10)-10(-8) mol) were almost abolished by L-NAME and L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M), although L-NOARG (3 x 10(-5) M) was significantly less potent than L-NAME (3 x 10(-5) M) as an inhibitor of vasodilator responses to 5-HT (5 x 10(-8) mol). 3. The vasodilator responses evoked by substance P (5 x 10(-12)-5 x 10(-9) mol) were reduced in the presence of L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) M). The response to substance P was almost abolished by L-NAME and L-NOARG (both at 10(-4) M). 4. The amplitude of the vasodilator responses to ATP (5 x 10(-11) and 5 x 10(-9)-5 x 10(-7) mol) was little affected by either L-NAME or L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M).7. It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibiting the vasodilator actions of 5-HT and ATP in this preparation.
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PMID:Effects of nitric oxide synthase inhibitors, L-NG-nitroarginine and L-NG-nitroarginine methyl ester, on responses to vasodilators of the guinea-pig coronary vasculature. 138 16

The possibility that nitric oxide (NO) could have a role in the modulation of inflammatory oedema formation was investigated in rat skin using selective inhibitors of NO synthesis. Intradermally injected substance P (0.03-1 nmol) induced oedema which was inhibited by concurrent administration of the inhibitor of NO synthesis L-NG-nitro arginine methyl ester (L-NAME), but not by the enantiomer D-NAME. L-Arginine reversed the inhibitory effect of L-NAME. A second inhibitor of NO formation, L-NG-monomethyl arginine (L-NMMA), had a similar inhibitory effect on substance P-induced oedema. The results suggest that endogenous NO has a modulatory role in oedema formation induced by mediators of increased microvascular permeability.
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PMID:Evidence that endogenous nitric oxide modulates oedema formation induced by substance P. 170 19

Nerve-induced vasodilatation was studied by intravital microscopy of the rabbit tenuissimus muscle, pretreated with pancuronium, phentolamine, and guanethidine. Nerve stimulation of the tenuissimus nerve induced a vasodilatation which was frequency and pulse duration-dependent and insensitive to atropine and propanolol but abolished by tetrodotoxin. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), but not its enantiomer, D-NAME, markedly inhibited the vasodilation induced by nerve stimulation or by exogenous substance P or neurokinin A. Vasodilatation due to calcitonin gene-related peptide, prostaglandin E2 or nitroprusside was unaffected. The substance P antagonist, spantide (30 microM), significantly attenuated nerve-induced vasodilatation, in parallel with L-NAME. Our results indicate that nerve-induced vasodilatation in skeletal muscle can be attributed to the release of substance P and/or other tachykinins and that nitric oxide subsequently mediates the response to endogenous tachykinins released from nerves.
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PMID:Nerve-induced tachykinin-mediated vasodilation in skeletal muscle is dependent on nitric oxide formation. 172 18

Kainic acid (KA)-sensitive receptors are located on primary afferent C-fibers. Behavioral sensitization to each of four repeated injections of KA appears to involve activation of primary afferent C-fibers based on its susceptibility to capsaicin pretreatment. Hyperalgesia, thought to involve transmission along C-fibers, is sensitive to pharmacologic manipulation of nitric oxide (NO). We tested the hypothesis that KA activates C-fibers, either directly or indirectly, by a mechanism that involves NO. Pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, inhibited KA sensitization whereas D-NAME, the inactive isomer, failed to mimic this action. D-Arginine also inhibited sensitization to KA, whereas L-arginine, a NO precursor, was inactive when administered alone but reversed the inhibitory effect of L-NAME. Methylene blue, which inhibits guanylyl cyclase and NO synthase, attenuated KA sensitization, suggesting that cyclic GMP synthesis may also be involved in this phenomenon. Reduced hemoglobin, which sequesters NO in the extracellular space, attenuated KA sensitization, indicating that the effect of NO is brought about in structures adjacent to cells in which it is synthesized. This convergence of data is consistent with the mediation of behavioral sensitization to KA by NO. KA sensitization has been shown to involve an action of the NH2 terminus of substance P (SP) and NO may thus mobilize SP. Consistent with this, in the presence of SP(1-7), methylene blue was no longer able to inhibit sensitization to KA, suggesting that NO evokes, rather than results from, mobilization of SP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sensitization to the behavioral effect of kainic acid in the mouse is mediated by nitric oxide. 747 37

The present study was undertaken to investigate the in vivo effects of nitric oxide (NO) mediating agents injected intracavernosally on penile erection in cats. All NO donors increased the cavernosal pressure and penile length in a dose-dependent manner. The maximal effects on cavernosal pressure and penile length induced by s-nitrosocysteine (NO-CYS) and s-nitroso-n-acetylpenicillamine (SNAP), respectively, were 8-fold and 5-fold increases in pressure, and 45% and 34% increases in length when compared with baseline values. These changes were comparable to that caused by the control drug combination (papaverine, phentolamine and prostaglandin E1). The effects of acetylcholine (ACh) and substance P on cavernosal pressure and penile length were less than those obtained with the control drug combination, NO-CYS (p < 0.01), or SNAP (p < 0.05). N omega-nitro-l-arginine-methyl-ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, significantly decreased the effects of NO-CYS, ACh and substance P on penile erection. This in vivo study with NO donors and an NOS inhibitor suggests that NO is a mediator of penile erection in cats.
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PMID:Nitric oxide mediates penile erection in cats. 750 45

This study examined the influence of overnight storage on endothelium-independent contractions to 5-hydroxytryptamine (5-HT), endothelium-dependent contractions to NG-nitro-L-arginine methyl ester (L-NAME), and endothelium-dependent relaxations to substance P (SP) and L-arginine, using the porcine isolated splenic artery. In endothelium-intact (E+) segments from fresh porcine isolated splenic arteries or segments from the same vessels stored overnight at 4 degrees C, either in Krebs-Henseleit saline or in Krebs-Henseleit saline containing 1 mM L-arginine, 5-HT caused concentration-related contractions that were similar under all three conditions. Overnight storage enhanced contractions of the splenic artery to L-NAME, an effect not observed if the vessels were co-stored with 1 mM L-arginine. L-NAME failed to contract endothelium-denuded (E-) segments from fresh tissues or tissues stored overnight, indicating that its constrictor effects were endothelium-dependent. SP caused concentration-related, endothelium-dependent relaxations of the splenic artery that were inhibited by 100 microM L-NAME, indicating that the relaxations could be attributed to the stimulated release of NO from endothelial cells. Established contractions to 100 microM L-NAME in E+ segments from fresh tissues, or segments from the same tissues stored overnight at 4 degrees C, either in Krebs-Henseleit saline or in Krebs-Henseleit saline containing 1 mM L-arginine, were all reversed by 1 mM L-arginine to similar extents, indicating that overnight storage did not affect endothelium-dependent dilator responses to L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Overnight storage of the porcine isolated splenic artery enhances endothelium-dependent contractions to NG-nitro-L-arginine methyl ester without impairing endothelium-dependent dilator function. 751 Dec 18

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

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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