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)

The modulatory role of endogenous nitric oxide (NO) on pulmonary edema induced by acetylcholine (ACh), capsaicin, substance P (SP) and 5-hydroxytryptamine (5-HT) was investigated by using an inhibitor of NO synthase, N-omega-nitro-L-arginine (L-NNA). The effects of endogenous NO on the hemodynamic response to ACh, 5-HT and SP were also investigated. The capillary filtration coefficient (Kf,c), the total pressure gradient (delta Pt) and its four components [arterial (delta Pa), pre- (delta Pa') and post-capillary (delta Pv'), and venous gradient (delta Pv)] were evaluated on isolated, ventilated, perfused rabbit lungs. ACh (10(-8) to 10(-4) M) and SP (10(-10) to 10(-6) M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4) M) and 5-HT (10(-4) M) also increased this parameter. L-NNA (10(-4) M) completely inhibited the effects of ACh and capsaicin on the Kf,c, without preventing the effects of SP and 5-HT. ACh induced a concentration-dependent vasoconstriction in the precapillary segment. Pretreatment with L-NNA enhanced this increase in delta Pa' but also increased delta Pv' and delta Pv. 5-HT increased delta Pt and delta Pa proportionally to the concentration. This effect was enhanced by L-NNA, which also increased delta Pa'. SP had no significant hemodynamic effect. Pretreatment with L-NNA did not modify the response to SP. Sodium nitroprusside (10(-5) M) induced a left shift of the concentration-response curve to ACh on the Kf,c, although it did not change the response to SP. Sodium nitroprusside also inhibited the hemodynamic effect of ACh. It was concluded that endogenous NO is involved in ACh-and capsaicin-induced edema via a prejunctional stimulatory effect on the C-fibers. Endogenous NO can also modulate ACh- and 5-HT-induced vasoconstriction by exerting a vasodilator action on the whole pulmonary vascular bed.
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PMID:Endogenous nitric oxide modulates acetylcholine-induced edema and vasoconstriction in isolated perfused rabbit lungs. 754 68

Evidence from our previous work suggests that neurogenic mediators contribute to the inflammation following ultraviolet (UV) irradiation of the skin. We have investigated whether calcitonin gene-related peptide (CGRP), substance P and nitric oxide (NO) participate in the cutaneous inflammatory reaction of the rat hind paw and ear to UV irradiation. Skin blood flow was measured by laser Doppler technique. Oedema was quantified using a spring loaded micrometer to measure ear thickness. UV irradiation of the rat skin lead to a long lasting increase in skin blood flow. This increase was dose dependently attenuated by the CGRP receptor antagonist CGRP-(8-37) (0.15 nmol in 25 microliters to 6.0 nmol in 25 microliters, s.c.) up to 51% with a maximum of effectiveness at 24 h post irradiation. The inhibitor of NO synthase NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 25 nmol in 25 microliters, s.c.) attenuated skin blood flow by 38%. Concurrent injections s.c. of CGRP-(8-37) (1.5 nmol in 12.5 microliters) and L-NAME (25 nmol in 12.5 microliters) demonstrated an augmentive effect in attenuating skin blood flow. The tachykinin NK1 receptor antagonist CP-96,345 (6.0 nmol in 25 microliters, s.c.) attenuated skin blood flow by 27%. NG-Nitro-D-arginine methyl ester hydrochloride (D-NAME) and CP-96.344 showed no effects on skin blood flow after UV irradiation. CGRP-(8-37) (0.6 nmol in 10 microliters) i.d. and L-NAME (10 nmol in 10 microliters) i.d. had no effect of oedema formation after UV irradiation. Furthermore, post UV irradiation enhanced CGRP- and NO synthase-immunoreactivity in nerve fibres in the exposed skin area were visible. Taken these findings together we suggest the involvement of the neuropeptides CGRP and substance P and of neuronal NO on the vasodilatory component of the UV-induced inflammatory reaction of the rat skin. CGRP contributing to UV-induced vasodilation acts in an endothelial NO-independent manner.
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PMID:Calcitonin gene-related peptide, substance P and nitric oxide are involved in cutaneous inflammation following ultraviolet irradiation. 754 83

The sensory and motor fibres of the spinal cord and the relative centres of integration were studied during ageing. Sections of spinal cord and ganglia from C8 to T12 of rats aged 6 and 24 months were treated using several techniques: Nissl, NADPH-diaphorase, and antibodies to enkephalins, substance P and neuropeptide Y. Nissl staining of the C8 segment showed that in the aged rat the dorsal horn was more oblique and narrow, the central canal was enlarged, the cellular density was reduced, and the neurons of the intermediolateral and ventral horns and of lamina IV were smaller. The total number of NADPH-diaphorase-positive cells of C8 segment was similar in the adult and in the aged rats. However, in the aged rat the number of cells was reduced in laminae I, II, III, VII and IX, remained the same in laminae V, VI and X, and was increased in laminae IV and VIII, and in the intermediolateral and intermediomedial horns. In the adult rat, we saw a greater number of cells with a lower expression of the enzyme. The area of the cells in laminae V and IX was reduced in the aged rat. In the C8 segment substance P was present in laminae I and II: in the aged rat the immunoreactivity was reduced and more diffuse. Enkephalins are present in laminae I, II and III, with a reduced immunoreactivity in the aged rat. NPY is present in the central canal in the adult rat and, is also present in laminae I and II in the aged rat.
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PMID:Neuronal populations in the spinal cord during ageing. 757 82

In order to determine whether nitric oxide (NO) acts directly upon nerve terminals to regulate the synaptic transmission at the level of spinal cord, effects of NO-donors on release of substance P (SP) and glutamic acid (Glu) were investigated by superfusion of synaptosomes prepared from the rat spinal cord. Basal levels of endogenous SP and Glu release were 5.99 +/- 2.50 fmol/min/mg of protein and 26.2 +/- 4.8 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCI evoked 2.7- and 3.8-fold increases in SP and Glu release in a calcium-dependent manner, respectively. Sodium nitroprusside (NP) caused a reduction in the depolarization-evoked overflow of SP in a concentration-dependent manner without affecting its basal release, although it failed to affect either basal or evoked release of Glu. The reduction in SP overflow was also observed by the perfusion with S-nitroso-N-acetyl-penicillamine or membrane-permeable cyclic GMP, but not with cyclic AMP. NP caused the concentration-dependent increases in cyclic GMP levels in synaptosomes. Together with reports that excitatory amino acids stimulate NO synthase and release NO in the spinal cord, these data suggest that there may be an interaction between nerve terminals containing Glu and SP, and that NO may directly participate in the regulation of synaptic transmission in SP-containing nerve terminals, which may be mediated through the activation of guanylate cyclase and the increase in cyclic GMP levels.
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PMID:Nitric oxide regulates substance P release from rat spinal cord synaptosomes. 759 89

To examine the effect of tachykinins on Cl secretion across tracheal mucosa and the possible contribution of nitric oxide (NO) formation to their actions in vivo, we measured Cl diffusion potential difference (Cl-PD) with a high-impedance voltmeter in the presence of amiloride. Superfusion of each neurokinin A (NKA) and substance P (SP) increased Cl-PD in a concentration-dependent fashion, whereas neurokinin B (NKB) had no effect, with the rank order of potency being NKA > SP >> NKB. The tachykinin-induced increase in Cl-PD was inhibited by the NO synthase inhibitor NG-nitro-L-arginine methylester (L-NAME), an effect that was reversed by L-arginine but not by D-arginine. These results suggest that tachykinins increase Cl secretion across rabbit trachea from the submucosa toward the lumen via stimulation of NK2 receptors and that NO formation may be involved in at least part of this process.
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PMID:[Role of nitric oxide in tachykinin-induced increase in Cl diffusion potential difference of rabbit tracheal mucosa]. 759 41

The distribution of NO synthase (NOS) immunoreactive nerves and the possible co-existence with other neurotransmitters were investigated in the pig lower urinary tract. NOS immunoreactive nerves were found in the muscle layer, in the lamina propria and around blood vessels. The density of NOS immunoreactive nerves was more prominent in the trigone and urethra than in the detrusor. All parts of the lower urinary tract were supplied by numerous acetylcholine esterase (AChE) positive nerves. The number of adrenergic nerves in the trigone and urethra was moderate to rich, whereas only very few adrenergic nerves were demonstrated in the detrusor. A low to moderate number of nerve fibres containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) were observed in the trigone and urethra, while very few were found in the detrusor. A small number of nerves, confined to the trigone and urethra, were stained for calcitonin-gene-related peptide, somatostatin and leu-enkephalin. Nerve fibres exhibiting immunoreactivity to bombesin/gastrin releasing peptide, gastrin/cholecystokinin, substance P or neurokinin A were virtually absent. Co-localization studies revealed that some NOS-immunoreactive nerves also stained for NPY, VIP or AChE. The present study shows that nitrergic nerves are present in the pig lower urinary tract in a density lower than the cholinergic, but higher than any of the studied peptidergic nerves. Coinciding localization of NOS-positive nerves with nerves expressing AChE, VIP and NPY suggests that NO may have a role as a messenger in the lower urinary tract directly and by interaction with other transmitters.
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PMID:Co-existence of nitrergic, peptidergic and acetylcholine esterase-positive nerves in the pig lower urinary tract. 761

In isolated porcine coronary arteries, acetylcholine elicited contractions that were potentiated by endothelium denudation. In endothelium-intact strips, the contraction deteriorated by repeated trials and was reversed to a relaxation. NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor, abolished the relaxation or reversed it to a contraction. Endothelium-dependent relaxations caused by serotonin were also reversed to a contraction by treatment with L-NA. Relaxations caused by substance P were dependent on the endothelium and were abolished by oxyhemoglobin; however, L-NA did not completely abolish the relaxation. It may be concluded that porcine coronary arteries respond to acetylcholine with contractions by a direct action on smooth muscle that are minimized by stimulated release of NO from the endothelium. It appears that the relaxation caused by serotonin is due to NO released from the endothelium, whereas the substance P-induced relaxation is associated mainly with endothelium-derived NO produced by NO synthase sensitive to L-NA and also with NO produced via a L-NA-resistant process or via a pathway distinct from that through NO synthase.
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PMID:Mechanisms of endothelium-dependent responses to vasoactive agents in isolated porcine coronary arteries. 767 56

The mechanism of action of endogenous tachykinins [substance P (SP) and neurokinin A and B (NKA and NKB)] and of receptor-specific tachykinin analogues (SP methyl ester (SPME), [beta-Ala8]NKA-(4-10), and senktide) was examined in circular muscle of guinea pig stomach. Cross-desensitization studies confirmed that SPME and SP interacted with NK-1 receptors, [beta-Ala8]NKA-(4-10) and NKA with NK-2 receptors, and senktide and NKB with NK-3 receptors. NK-1 and NK-3-receptor agonists induced relaxation and stimulated vasoactive intestinal peptide (VIP) release and nitric oxide (NO) production: tetrodotoxin abolished VIP release, NO production, and relaxation, converting the response to NK-1-receptor agonists to contraction; the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) abolished NO production, partly inhibited VIP release (56-64%, P < 0.01), and abolished relaxation; the VIP antagonist VIP-(10-28) partly inhibited NO production (73-74%, P < 0.001) and relaxation (56-58%, P < 0.01); and atropine augmented relaxation by 28-35% (P < 0.01). The pattern of inhibition implied that: 1) relaxation was mediated by VIP and NO; 2) VIP release was partly dependent on NO production, since it was strongly inhibited by L-NNA; and 3) NO was largely produced by the action of VIP on muscle cells, since it was strongly inhibited by VIP-(10-28). NK-2-receptor agonists elicited only contraction that was not affected by tetrodotoxin; these agonists also inhibited VIP release, NO production, and relaxation induced by NK-1- and NK-3-receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional difference between SP and NKA: relaxation of gastric muscle by SP is mediated by VIP and NO. 768 82

Purposes of this study were to determine whether: (1) nitric oxide is involved in endothelium-dependent relaxation in helical strips of dog cerebral arteries; (2) relaxing factor distinct from NO is also involved, and (3) susceptibility to NG-nitro-L-arginine (L-NA), an NO synthase inhibitor, of the response to mediators liberating NO from the endothelium and nerve differs. Changes in isometric tension were recorded. In the strips contracted with prostaglandin F2 alpha, substance P and arginine vasopressin produced a relaxation which was abolished or reversed to a contraction by endothelium denudation. The relaxations were not influenced by indomethacin but were suppressed dose-dependently by L-NA, as was the response to nicotine that stimulates the non-adrenergic, non-cholinergic vasodilator nerve and liberates NO. The inhibitions were reversed by L- but not D-arginine. NO (acidified NaNO2)-induced relaxations were not reduced by L-NA. The inhibitory effect was greater in the responses to vasopressin than substance P; however, there was no significant difference in the response to nicotine vs. the peptides. Substance P increased the level of cyclic guanosine monophosphate (GMP) in the artery strips with the intact endothelium, the effect being abolished by endothelium denudation, L-NA and oxyhemoglobin. Relaxations caused by adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were dependent partially on the endothelium. Treatment with L-NA attenuated the ATP-induced relaxation in the strips with endothelium but did not alter the response of denuded strips.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebroarterial relaxations mediated by nitric oxide derived from endothelium and vasodilator nerve. 768 37

The vasodilating effect of substance P (SP) at the microvascular level is endothelium-dependent. In the present study we evaluated whether SP activates nitric oxide (NO) production by venular endothelial cell. We evaluated NO activation by measuring cyclic GMP levels in cultured endothelial cells isolated from coronary postcapillary venules of bovine origin (CVEC). Our results indicate that 5 min exposure of CVEC to 10 nM SP doubled basal cyclic GMP levels. Cell treatment with the NO synthase inhibitor L-NMMA reduced the basal levels of cyclic GMP and abolished the effect of SP but did not modify the increase in cyclic GMP in response to exogenous NO. These data indicate that a) microvascular endothelium responds in an autocrine fashion to NO with increased cyclic GMP levels, b) SP activates cyclic GMP pathway through NO production.
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PMID:Substance P increases cyclic GMP levels on coronary postcapillary venular endothelial cells. 769 Apr 46


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