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)

N omega-Nitro-L-arginine methyl ester has been reported to have muscarinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, undertaken to compare the inhibitory effects of N omega-nitro-L-arginine methyl ester with those of N omega-nitro-L-arginine on baseline tone and on vasodilator responses to acetylcholine, bradykinin, and substance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine in doses of 100 mg/kg i.v. increased baseline tone in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator agents following administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine did not differ significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine but did not alter responses to bradykinin or substance P. The similarity in the inhibitory effects of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine on responses to acetylcholine, bradykinin, and substance P suggest that the L-arginine analog, N omega-nitro-L-arginine, as well as the methyl ester of N omega-nitro-L-arginine, are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascular bed of the cat.
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PMID:Comparative effects of N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance P. 751 84

Several studies have shown that the undecapeptide, substance P, alters behaviour following central or peripheral administration in the rat. Here we report that L-arginine administration increases substance P-induced locomotion and changes in food intake in rats. NG-Nitro-L-arginine methyl ester, a specific inhibitor of nitric oxide synthase, reduces substance P-induced effects. These results suggest that endogenous nitric oxide plays a role in the modulation of the catecholaminergic effect of substance P on motor behaviour. They also clarify the mechanism underlying food intake induced by substance P.
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PMID:Endogenous nitric oxide modulates behavioural effects elicited by substance P in rat. 753 5

Human umbilical vessels are devoid of nerves and therefore endothelial cells may play an important role in the control of fetoplacental blood flow. In this study we examined the pharmacological effects of various substances, known to produce endothelial-mediated vasodilation in many blood vessels, on the human umbilical artery and vein from legal terminations [mean gestational age, 15 (8-17) weeks; n = 12] and normal term vaginal deliveries [mean gestational age, 39 (38-41) weeks; n = 12]. Acetylcholine, adenosine 5'-triphosphate, the calcium ionophore A23187 and substance P had no effect on raised vascular tone, whereas sodium nitroprusside relaxed 5-hydroxytryptamine (5-HT) preconstricted, umbilical artery and vein from both early and late pregnancy. L-NG-Nitroarginine methyl ester (L-NAME) had no effect on basal tone or on high tone, after it was raised by 5-HT. Localization of nitric oxide synthase [NOS, type I (neuronal)] was examined in the same umbilical vessels using electron immunocytochemistry. No NOS-immunoreactive endothelial cells were observed in the umbilical vessels taken during early pregnancy. However, the percentage of NOS-immunoreactive endothelial cells in umbilical artery and vein from late pregnancy was 3 and 10 per cent, respectively. These results suggest that nitric oxide contributes little, if any, to the local control of umbilical blood flow throughout pregnancy, despite the presence of NOS-immunoreactivity in a subpopulation of endothelial cells in late pregnancy.
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PMID:Nitric oxide and human umbilical vessels: pharmacological and immunohistochemical studies. 763 9

The effect of inhibiting nitric oxide synthase (N omega-nitro-L-arginine) on plasma extravasation induced by intravenously administered substance P, [pGlu5,Me-Phe8,Sar9]substance P-(5-11) or prostaglandin E2 was examined. Control rats were more responsive than diabetic rats to both substance P and [pGlu5,Me-Phe8,Sar9]-substance P-(5-11). N omega-Nitro-L-arginine blocked the actions of substance P on dorsal skin, but potentiated those of [pGlu5,Me-Phe8,Sar9]substance P-(5-11) in control rats. In diabetic rats N omega-nitro-L-arginine, which did not affect the actions of the substance P analogue, exerted complex effects on substance P induced plasma extravasation giving potentiation in the tongue, inhibition in bronchioles, and no effect in other tissues. N omega-Nitro-L-arginine inhibited prostaglandin E2 induced extravasation in control, but not diabetic rats. The altered plasma extravasation in diabetic rats may be due to diabetes induced alterations in nitric oxide synthesis or in the responses of the endothelial cells to nitric oxide.
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PMID:Altered vascular permeability responses to substance P in diabetic rats: interactions with a nitric oxide synthesis inhibitor. 769 56

A role for nitric oxide in the H3-histaminergic agonist-induced inhibition of the non-adrenergic, non-cholinergic (NANC) contraction has been studied in guinea-pig perfused bronchioles. (R)-alpha-Methylhistamine ((R)-alpha-MeHA), an agonist for H3 receptors, inhibited the NANC contraction induced by electrical field stimulation. NG-Nitro-L-arginine methyl ester (L-NAME) (50 microM), an inhibitor of nitric oxide synthesis, blocked the effect of (R)-alpha-MeHA. The effect of L-NAME was reversed by L-arginine (50 microM). L-NAME, L-arginine or (R)-alpha-MeHA were without effect on exogenous substance P- or neurokinin A-induced contractile responses of the perfused bronchioles. These results show that an H3-agonist inhibited the release of neurotransmitters in NANC nerve endings of guinea-pig perfused bronchioles presumably by production of nitric oxide.
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PMID:NG-nitro-L-arginine methyl ester inhibits the effect of an H3-histaminergic receptor agonist on NANC contraction in guinea-pig perfused bronchioles. 802 8

The role of nitric oxide in inflammatory responses to substance P and other mediators of inflammation was examined in rat skin microvasculature in a blister base raised on the hind footpad. Superfusion of substance P (1 microM) over the blister base caused an increase in plasma extravasation and a vasodilator response which was not maintained. N(G)-Nitro-L-arginine (100 microM), an inhibitor of nitric oxide biosynthesis, attenuated vasodilatation and plasma extravasation due to substance P. The inactive isomer N(G)-nitro-D-arginine was without effect. Neurokinin A (1 microM), 5-hydroxytryptamine (1 microM), ATP (50 microM) and vasoactive intestinal polypeptide (1 microM) elicited vasodilation, which for vasoactive intestinal polypeptide was maintained even after washout. 5-Hydroxytryptamine and neurokinin A, but not ATP or vasoactive intestinal polypeptide, significantly increased plasma extravasation. Vasodilatation to neurokinin A, 5-hydroxytryptamine and ATP, and the increase in plasma extravasation due to neurokinin A and 5-hydroxytryptamine were unaffected by N(G)-nitro-L-arginine (100 microM), whereas vasodilation due to vasoactive intestinal polypeptide was significantly attenuated. These findings suggest that in rat skin microvasculature in vivo, nitric oxide is involved in vasodilator responses due to substance P and vasoactive intestinal polypeptide, and plasma extravasation due to substance P, but does not contribute significantly to vasodilatation induced by neurokinin A, 5-hydroxytryptamine or ATP, or the plasma extravasation induced by neurokinin A or 5-hydroxytryptamine.
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PMID:Role of nitric oxide in the actions of substance P and other mediators of inflammation in rat skin microvasculature. 866 4

1. In the progress of experiments aimed at evaluating the role of tachykinins as enteric nonadrenergic noncholinergic (NANC) transmitters, we noted that certain tachykinin receptor antagonists produce a relaxation of circular muscle strips in the rat small intestine. This study aimed to assess the nature of this response and to determine the receptor type involved. The majority of the experiments were performed in capsaicin- (10 microM for 15 min) pretreated mucosa-free circular muscle strips from the rat small intestine, in the presence of atropine (1 microM), guanethidine (3 microM) and indomethacin (10 microM). 2. Under isometric recording of mechanical activity, the tachykinin NK1 receptor antagonist SR 140,333 (0.1 microM) had no effect on resting tone or spontaneous activity in duodenal or ileal circular muscle strips. The NK2 receptor antagonists, MEN 10,627 (0.1 microM) and GR 94,800 (0.1 microM) produced, after a delay of 10-15 min, a relaxation which averaged 61 +/- 3 and 57 +/- 6% (n = 6 and 4, respectively) of the maximal response (Emax) to isoprenaline (1 microM). The effect of maximal concentrations of MEN 10,627 and GR 94,800 when applied together was non-additive. The relaxant effect of MEN 10,627 (0.1 microM) was similar in the absence and presence of apamin (0.3 microM) and L-nitroarginine (100 microM). 3. Under isotonic recording of mechanical activity, MEN 10,627 (10 nM-1 microM) produced a concentration- and time-related relaxation of duodenal strips. The maximal relaxation averaged 72 +/- 4 and 69 +/- 4% (n = 5 each) of Emax to isoprenaline (1 microM) and was achieved 15-20 or 20-30 min after application of 1.0 or 0.1 microM MEN 10,627, respectively. 4. Duodenal strips were relaxed by other NK2 receptor selective antagonists (values in parentheses are % of Emax to isoprenaline at the given concentration of antagonist) GR 94,800 (69 +/- 3% at 1 microM, n = 4), SR 48,968 (60 +/- 3% at 1 microM, n = 4) and MDL 29,913 (66 +/- 4% at 1 microM, n = 4). SR 48,965 (1 microM), the inactive enantiomer of SR 48,968, was without effect. The NK1 receptor selective antagonists, SR 140,333 (0.1 microM), FK 888 (10 microM) RP 67,580 (1 microM) and GR 82,334 (10 microM) were also without effect (n = 4-5). 5. A cocktail of peptidase inhibitors, thiorphan, bestatin and captopril (1 microM each) had no significant effect on tone or spontaneous activity of duodenal strips. In the presence of peptidase inhibitors, MEN 10,627 (1 microM) produced a relaxation of duodenal strips (72 +/- 6% of Emax to isoprenaline, n = 5), whilst GR 82,334 (10 microM, n = 6) had no significant effect. 6. The relaxant response to MEN 10,627 was preserved in mucosa-free strips not pre-exposed to capsaicin. Tetrodotoxin (1 microM), saxitoxin (1 microM), hexamethonium (100 microM) and omega-conotoxin (0.1 microM) had no significant effect on the resting tone of duodenal strips nor did they affect the relaxation to MEN 10,627. L-Nitroarginine (100 microM) increased the tone of the strips but did not affect the response to MEN 10,627. Nifedipine (1 microM) relaxed the strips by 62 +/- 4% (n = 4), but in its presence a small relaxant effect to MEN 10,627 (26 +/- 5%, n = 4) was still evident. 7. Under isotonic recording of mechanical activity along the longitudinal axis, MEN 10,627 (1 microM) produced a slowly developing relaxation (39 +/- 3% of Emax to isoprenaline; n = 6) of whole segments of rat duodenum. When similar experiments were performed on whole segments of rat proximal colon MEN 10,627 had no effect. 8. The present findings document the observation that tachykinin NK2 receptors contribute to the maintenance of resting tone of the rat isolated small intestine. We found no evidence to suggest that this effect follows the blockade of the contractile effect of spontaneously released endogenous tachykinins. The present findings raise the possibility that constitutively active NK2 receptors account for the relaxant effect produced by NK2 receptor ant
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PMID:Evidence that tachykinin NK2 receptors modulate resting tone in the rat isolated small intestine. 881 52

Several in vitro models of gastric relaxation have elucidated a role of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) in non-adrenergic, non-cholinergic (NANC) vagally mediated gastric relaxation. However, these models do not necessarily mimic the events leading to gastric relaxation in the whole animal. We have recently described a vagally mediated gastric relaxation evoked by micro-injection of substance P (SP) into the nucleus raphe obscurus (NRO). The present study was performed to elucidate whether this CNS-stimulated in vivo gastric relaxation involved acetylcholine, NO and VIP. Atropine (1 mg kg-1 i.v.), reduces both the rapid nadir and sustained gastric relaxation evoked by SP in the NRO, and the residual responses are abolished by NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg kg-1 i.v.), an NO synthase inhibitor. Blockade of NO synthase alone is not sufficient to abolish the effect of SP into the NRO on intragastric pressure. A VIP antagonist, [p-chloro-D-Phe6, Leu17]VIP (32 micrograms i.v.) alone, or with the addition of L-NAME, does not affect the nadir of the gastric relaxation in response to SP microinjected into the NRO; however, both antagonists reduce the CNS-evoked sustained intragastric pressure relaxation. We conclude that, in CNS-evoked gastric relaxation, inhibition of cholinergic pathways is potentially important for both the rapid nadir and sustained gastric relaxation, and both NO and VIP contribute to sustained gastric relaxation.
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PMID:Contribution of acetylcholine, vasoactive intestinal polypeptide and nitric oxide to CNS-evoked vagal gastric relaxation in the rat. 895 35

The lipopolysaccharide (endotoxin) of gram-negative bacteria has systemic effects in animals and man. Our aim was to investigate the effects of E. coli lipopolysaccharide on motility and transit through the small intestine in rats and to analyze plasma and tissue concentrations of intestinal neuropeptides. When lipopolysaccharide (20-160 micrograms/kg) was administered intravenously, the migrating myoelectric complex was replaced by spike bursts accompanied by rapid transit. Tissue concentrations of substance P and neurokinin A decreased, while plasma levels of calcitonin gene-related peptide increased N omega-Nitro-L-arginine, N omega-L-arginine methyl ester, dexamethasone, or indomethacin prevented these changes in myoelectric activity and tissue contents of neuropeptides. All of these compounds, except indomethacin, prevented the increased rate of transit. Thus, lipopolysaccharide changes motility through the nitric oxide and arachidonic pathways, resulting in rapid transit through the gut.
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PMID:Endotoxin actions on myoelectric activity, transit, and neuropeptides in the gut. Role of nitric oxide. 928 29

The relationship between relaxation produced by acetylcholine (ACh) or substance P (SP) and tissue cyclic GMP content was investigated in the isolated guinea-pig aorta. ACh and SP relaxed aortic rings precontracted with noradrenaline (NA) or high-K solution ([K+]o = 38.8 mM), in an endothelium-dependent manner. The amplitude of relaxation was larger for SP than for ACh. Nitroarginine inhibited ACh-induced but not SP-induced relaxation in NA-contraction, while this chemical inhibited both ACh- and SP-induced relaxations in high-K contraction. The tissue cyclic GMP content was not changed by nitroarginine or by removal of endothelial cells, but was elevated by stimulation with NA, ACh or SP by a factor of about 3, 5 or 11 times, respectively. These actions of ACh or SP were endothelium-dependent, and were inhibited by nitroarginine and remained unaltered by high-K solution. Thus, ACh and SP relax muscles indirectly by releasing endothelial factors, and the former by releasing mainly an endothelium-derived relaxing factor (EDRF), and the latter by releasing EDRF and other unidentified factors. As the relaxing actions of the latter factors are inhibited by high-K solution with no relation to the production of cyclic GMP, an involvement of hyperpolarizing factor, possibly EDHF, is suggested.
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PMID:Comparison of the relaxing actions of acetylcholine and substance P in smooth muscle of the guinea-pig aorta. 940 18


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