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 mediator accounting for the major relaxant responses to electrical field stimulation of human airways was previously identified as nitric oxide (NO). In the present study, we examined the distribution of the neuronal isoform of the NO-generating enzyme, nitric oxide synthase (bNOS, type I NOS) in nerve fibers of the human airways (trachea, large and small bronchi, bronchioli) as well as in human intrinsic and sensory ganglia of airway innervation by means of quantitative histochemistry (NADPH-diaphorase technique) and immunohistochemistry. Correlation with substance P (SP) and vasoactive intestinal peptide (VIP) was performed by double-labeling immunohistochemistry. NOS-containing nerve fibers were found to be present in the airway smooth muscle, around submucosal glands, around blood vessels and, very rarely, in the lamina propria. The innervation density of airway smooth muscle by NOS-containing nerve fibers decreased significantly from trachea to large-diameter bronchi to small-diameter bronchi, whereas NOS-containing nerve fibers were completely absent from bronchioli. Colocalization of NOS with VIP but not with SP was frequent in these nerve fibers. In airway intrinsic ganglia, the number of NOS-containing neuronal cell bodies increased from 57% in the trachea up to 83% in small bronchi. Around these perikarya, many nerve fibers displaying VIP-immunoreactive (VIP-IR) or SP-IR were found. In the superior vagal sensory (i.e., jugular) ganglion most of the neuronal cell bodies contained either NOS-IR or SP-IR; a colocalization of both was not as frequent. These data contribute to the understanding of the morphologic basis underlying the functional differences of the neural relaxant responses mediated by NO at different levels of the airway tree.
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PMID:Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory ganglia of man. Correlation with neuropeptides. 868 Jun 82

To characterize the innervation of the cynomolgus monkey (Macaca fascicularis) Meibomian (tarsal) glands, upper lids of six cynomolgus monkeys were investigated with electronmicroscopical and double-labeling immunocytochemical methods. Antibodies against calcitonin gene-related peptide (CGRP), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY), nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for NADPH-diaphorase (NADPH-d) histochemistry. Staining for PGP 9.5 and electron microscopy showed that Meibomian gland acini were surrounded by a network of unmyelinated nerves and terminal varicose axons. The terminals contained small agranular (30-60 nm) and large granular vesicles (65-110 nm), and were observed in close contact with the basal lamina of the acini, but never internally to the basal lamina. Meibomian axons showed like-immunoreactivity (LI) for the neuropeptides SP, CGRP, NPY, and VIP. In addition, the axons stained for TH, DBH, NOS, and NADPH-d. VIP-LI, NOS- and NADPH-d-positive axons appeared to be more numerous, TH- and DBH-positive axons more rare than others. Most SP-LI axons were double-labelled for CGRP-LI, some for VIP-LI or NPY-LI. In addition, some VIP-LI axons were double-labeled for NPY-LI. NPY/VIP-LI and NPY/SP-LI axons were only observed close to the Meibomian acini. Conversely, NPY-LI colocalized with TH-IR or DBH-IR predominated in perivascular nerves of Meibomian gland vasculature. The close association of varicose axons with the acini of Meibomian glands indicates that nervous signals modulate meibomian secretion. Meibomian gland nerve fibers in the cynomolgus monkey appear to utilize various neuropeptides, catecholamines and nitric oxide as transmitter substances, and seem to derive from the pterygopalatine, superior cervical and trigeminal ganglion respectively.
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PMID:Characterization of Meibomian gland innervation in the cynomolgus monkey (Macaca fascicularis). 869 72

We have previously shown that substance P (SP), microinjected into the caudal nucleus raphe obscurus (nROb) of the rat decreases intragastric pressure via a vagally mediated pathway. Recent studies from this laboratory demonstrated that nitric oxide (NO) synthase is present in the dorsal vagal complex (DVC) and NO synthase blockade in the DVC of the rat with NG-nitro-L-arginine methyl ester (L-NAME) evokes increases in intragastric pressure. Since the nROb controls gastric vagal outflow through the DVC, we tested the hypothesis that NO in the DVC is a mediator of inhibitory effects of SP on gastric motor function in the nROb. Substance P (135 pmol) was microinjected into the nROb 3-6 min after bilateral microinjections of L-NAME (45 nmol per site) into the DVC of chloralose-anesthetized rats were started. Changes in the area of the response for intragastric pressure on microinjection of SP after L-NAME did not differ from the effect of vehicle microinjected after L-NAME and were significantly lower when compared with the effect of SP microinjected after vehicle. We conclude that SP in the nROb release NO in the DVC to mediate the inhibitory effect on intragastric pressure.
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PMID:The inhibitory effect of substance P on gastric motor function in the nucleus raphe obscurus is mediated via nitric oxide in the dorsal vagal complex. 873 11

The presence and distribution of nitric oxide synthase (NOS)-immunoreactive nerve fibers associated with the guinea pig major cerebral arteries was studied by means of immunohistochemical, histochemical and ultrastructural techniques. Anterior arteries of the circle of Willis received a rich supply of perivascular nerve fibers containing NOS immunoreactivity while posteriorly localized arteries presented a moderate to sparse innervation. A double immunofluorescence staining technique revealed that NOS was localized in nerve fibers distinct from those displaying substance P or tyrosine hydroxylase. Combined immunofluorescence and histochemical staining of the same preparation indicated that NOS immunoreactivity was localized in putative cholinergic nerve fibers (identified by their acetylcholinesterase content) and that NADPH-diaphorase activity (a marker for NOS-containing neurons) was found in nerves which also possessed VIP immunoreactivity. The ultrastructural study revealed that NOS immunoreactivity was present in numerous nerve varicosities at the adventitial-medial border. These results suggest that NO and VIP co-exist in putative parasympathetic nerve fibers supplying the guinea pig cerebral arteries and may be release together in response to nervous stimulation.
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PMID:Nitroxidergic innervation of guinea pig cerebral arteries. 874 Jun 67

Recent pharmacological studies have shown that perivascular nerves can influence the development and function of vascular endothelial cells (ECs). However, morphological studies have not yet been carried out to investigate whether these functional changes are associated with changes in vasoactive substances in ECs. We used postembedding electron microscopy (EM) triple gold-labeling immunocytochemistry to study the effects of short-term sympathectomy (3 days after 6-hydroxydopamine [6-OHDA] treatment) and long-term sympathectomy (guanethidine and 8 days after 6-OHDA) on the distribution of vasoactive substances in ECs of the rat thoracic aorta. The post-embedding immunocytochemistry, which can detect levels of label in individual cells, showed that there was a significant decrease in endothelial NO synthase (NOS3)-labeled, serotonin (5-HT)-labeled, and substance P (SP)-labeled, but a significant increase in endothelin-1 (ET-1)-labeled, gold particles in ECs after long-term, but not after short-term (3-day), sympathectomy. In conclusion, our results show that long-term sympathectomy causes an increase in ET-1 and decrease in NOS3, 5-HT, and SP immunoreactivity in ECs of the thoracic aorta. Our data also indicate that postembedding EM triple gold-labeling immunocytochemistry is a valuable technique for quantitative studies of the content of vasoactive substances in ECs.
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PMID:Depression of endothelial nitric oxide synthase but increased expression of endothelin-1 immunoreactivity in rat thoracic aortic endothelium associated with long-term, but not short-term, sympathectomy. 875 10

The aims of the present study were to determine whether nerves that contain nitric oxide synthase (NOS), calcitonin gene-related peptide (CGRP) or substance P (SP) are present in the human vagina and, if so, to determine the pattern of innervation relative to that of other neurotransmitters, particularly vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Surgical specimens of vaginal tissue (n = 10) from pre- and postmenopausal women were fixed and processed for immunohistochemistry of peptides and NOS and for histochemistry of NADPH-diaphorase. SP-immunoreactive nerves were very sparse, being absent from 9 of the 10 tissue samples. For other peptides and NOS, the innervation of the deep arteries and veins was greater than that of blood vessels in the propria. Capillaries in the epithelial papillae also appeared to be innervated by nerves containing NOS, CGRP, NPY and VIP. Beneath the epithelium nerve fibres formed a subepithelial plexus; no nerve cell bodies were seen. The relative density of innervation by immunoreactive fibres was PGP-9.5 > NPY > VIP >> NOS > CGRP > SP. These results imply that nerves that utilise nitric oxide or NPY, VIP or CGRP as a neurotransmitter may play a role in controlling blood flow and capillary permeability in the human vagina. The origin and function of all these nerves is discussed.
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PMID:Innervation of vasculature and microvasculature of the human vagina by NOS and neuropeptide-containing nerves. 876 80

The endothelium takes part in the regulation of vascular tone through the production of endothelium-derived relaxing and contracting factors. The L-arginine pathway within endothelial cells in the blood vessel wall is the source of production of the endogenous nitrovasodilator, nitric oxide (NO). The NO molecule has one unpaired electron and readily reacts with oxygen, superoxide radicals, or transition metals. Therefore the measurement of the concentration of NO in biological systems is a challenging analytical problem. NO is formed from L-arginine via constitutive NO synthase. It is released under basal conditions and in response to mechanical stimuli such as shear stress and in response to receptor-operated agonists such as bradykinin, serotonin, ADP/ATP, thrombin, histamine and substance P. NO is the mediator of endothelium-dependent relaxation in the circulation and exerts its effects by activating soluble guanylyl cyclase in vascular smooth muscle, which in turn leads to the formation of cyclic guanosine monophosphate (cyclic GMP) and to relaxation. In addition to its effect on vascular smooth muscle, NO is also released albuminally to interact with circulating platelets. Increases in cyclic GMP in platelets are associated with a decreased adhesion and aggregation. In endothelial cells, NO inhibits its own production as well as that of the vasoconstrictor peptide endothelin-1. Thus, endothelium-derived NO, through its vasodilator and anti-aggregatory properties, prevents vasospasm and thrombus formation in the circulation and thereby helps to maintain blood flow to vital organs such as the heart. Under certain conditions such as inflammation, NO may also be formed via inducible nitric oxide synthase by smooth muscle cells, endothelium and monocytes. Therapeutic nitrates also exert their effects by releasing NO from their molecules and activating soluble guanylyl cyclase. Their effects are particularly pronounced in arteries in which the release of NO is inhibited or impaired or in the absence of the endothelium. Thus, the endothelial L-arginine pathway plays an important protective role in the local regulation of blood flow and through its vasodilator and antiplatelet properties. Nitrates can at least in part substitute the endogenous nitrovasodilator in disease states with impaired formation of NO.
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PMID:[Nitric oxide: the endogenous nitrate in the cardiovascular system]. 876 25

1. Incubation of proximal segments of the rat isolated duodenum with NG-nitro-L-arginine (L-NOARG; 3-100 microM) produced a concentration-dependent increase in both resting tone and the amplitude of the spontaneous contractions. These effects were attenuated by concurrent incubation with L-arginine (1 mM) but not D-arginine (1 mM). 2. These changes in resting tone and motility induced by L-NOARG (30 microM) were substantially reduced by concurrent incubation with tetrodotoxin (1 microM) or hexamethonium (10 microM), implicating the involvement of a local neuronal response. 3. The L-NOARG-induced increase in duodenal motility was not, however, inhibited by atropine (1 microM), guanethidine (6.4 microM) phentolamine (1 microM), or indomethacin (10 microM), indicating a non-cholinergic, non-adrenergic and non-prostanoid-mediated contractile response. 4. The NK1/NK2 tachykinin receptor antagonist, (D-Pro2, D-Trp7.9 substance P, 1-10 microM), and the NK2-receptor antagonists, MEN 10,207 and MEN 10,376 (1-5 microM), concentration-dependently reduced the effect of L-NOARG (30 microM) on spontaneous duodenal motility. 5. The resting tone and amplitude of the spontaneous contractions was likewise increased by incubation with NG-monomethyl-L-arginine (L-NMMA; 100-1000 microM). However, incubation with L-NMMA (100 microM) attenuated the actions of more potent L-NOARG (30 microM) on resting motility. 6. Administration of E.coli endotoxin (3 mg kg-1, i.v.) to the rat 5 h prior to tissue removal, at a time of known induction of NO synthase, reduced the amplitude of spontaneous contractions of the isolated duodenum, an effect inhibited by pretreatment of the rats with dexamethasone (1 mg kg-1) 2 h prior to endotoxin challenge. 7. These findings indicate a role of endogenous NO in the modulation of spontaneous tone and motility in the rat duodenum. Induction of NO synthase may result in a reduction in spontaneous motility of the tissue. By contrast, inhibition of constitutive NO biosynthesis unmasks a contractile response that is neuronally mediated and involves tachykinin NK2 receptors.
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PMID:Modulation by nitric oxide of spontaneous motility of the rat isolated duodenum: role of tachykinins. 883 54

Diaspirin cross-linked hemoglobin (DCLHbTM; Baxter Healthcare Corp., Round Lake, IL, USA) is undergoing clinical trials as a blood substitute. Administration of DCLHb is associated with an increase of mean arterial pressure in vivo and contraction of selected adult isolated blood vessels of from certain species in vitro. The mechanisms of these pressor effects may be due to scavenging of the endothelium derived relaxing factor, nitric oxide (NO), by hemoglobin. Unlike adult blood vessels, prostacyclin (PGI2) rather than EDNO is the important relaxing agent in human umbilical vessels. In this study, we examined if DCLHb had vasoconstrictor effects on isolated human umbilical vessels. Human umbilical veins and arteries were excised, cut into rings and placed in organ chambers filled with 25 ml Krebs-Ringer solution (37 degrees C). 5-hydroxytryptamine (5-HT, 0.01-10 microM) increased the tension of human umbilical arteries (HUA, from 0.4 +/- 0.2 g to 2.6 +/- 0.4g) and veins (HUV, from 0.8 +/- 0.4g to 2.5 +/- 0.4g) in a dose-dependent manner. DCLHb (0.01-10 microM) did not have a significant effect on HUA and HUV. Substance P (1 microM, via prostanoid synthesis) and nitroglycerin (NG, 1 microM) but not acetylcholine (ACh, 1 microM) caused relaxation of both HUA and HUV. The NO synthase inhibitor L-NA did not have significant effects on HUA and HUV. DCLHb did not alter 5-HT preconstricted tension of HUA and HUV. The basal cGMP contents of HUA and HUV were low. These results support our previous finding that DCLHb-induced vasoconstriction in isolated vessels is dependent primarily on the binding of NO by hemoglobin.
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PMID:Diaspirin cross-linked hemoglobin does not alter isolated human umbilical artery or vein tone. 892 31

Capsaicin has been previously shown to increase cochlear blood flow (CBF) in a dose-dependent manner. The aim of this study was to define the role of nitric oxide (NO) in capsaicin-induced changes in CBF. This was investigated in the anesthetized guinea pig, utilizing laser Doppler flowmetry. Application of capsaicin (64.8 and 6.48 nmol in 2 microliters of saline) to the round window membrane (RWM) caused increases in CBF (34 +/- 2.8% of baseline (BL) and 28 +/- 2.3% BL, respectively (P < 0.001)). Application of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg intravenously or topically to the RWM) reduced blood flow in the cochlea, as previously reported. After pretreatment with i.v. L-NAME, the effect of capsaicin on CBF was significantly decreased. With the dose of capsaicin at 64.8 nmol, the increase in CBF fell from 34 +/- 2.8% BL to 6.9 +/- 1.5% BL (P < 0.001), and at 6.48 nmol it fell from 28 +/- 2.3% BL to 4.8 +/- 1.6% BL (P < 0.001). RWM L-NAME application also decreased the capsaicin vasodilatation effect. A capsaicin dose of 64.8 nmol resulted in only a 10 +/- 2.5% BL increase in CBF, and with 6.48 nmol capsaicin the increase was 7.8 +/- 2.2% of BL (P < 0.001). Capsaicin-sensitive sensory neurons in other systems are generally known to release substance P (SP), which in turn elicits release of endothelium derived relaxing factor (NO). The results of this study indicate that NO is a mediator of capsaicin-sensitive sensory neuronal function in CBF regulation.
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PMID:Nitric oxide mediates capsaicin-induced increase in cochlear blood flow. 892 85


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