UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although considered as an intestinal motor stimulant, substance P can inhibit intestinal peristalsis via stimulation of tachykinin NK1 receptors. Since NK1 receptors are present on enteric nitrergic neurones, the contribution of nitric oxide (NO) to the peristaltic motor inhibition caused by tachykinins was examined in luminally perfused segments of isolated guinea-pig ileum. Substance P (100 nM) and the NK1 receptor agonist substance P methyl ester (100 nM) increased the intraluminal pressure threshold at which peristaltic contractions were elicited. This inhibitory influence on peristalsis was prevented by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (300 microM) in an enantiomer-selective manner. It is concluded that the substance P/NK1 receptor-mediated depression of intestinal peristalsis involves inhibitory motor pathways utilizing NO as a transmitter.
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PMID:Involvement of nitric oxide in the substance P-induced inhibition of intestinal peristalsis. 937 19

The autonomic nervous system is involved in different functions such as transduction of afferent sensory inputs, trophic actions, modulation of immunologic events and thermoregulation. In the present investigation, we studied the pattern of human autonomic skin innervation with special reference to its relation to blood vessels, hair follicles, sweat glands and sensory receptors. For the first time, two clinically important areas have been compared: the skin of the forearm and of the face. Using indirect immunohistochemistry, we analyzed the distribution of calretinin (CR), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), neurokinin A (NKA), vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS), tyrosine hydroxylase (TH), histamine, serotonin, enkephalin, and, enzyme histochemically, NADPH-diaphorase (NADPH-d). In the epidermis, we found nerve fibers containing SP, NKA and CGRP. In the dermis, SP-, CR-, VIP-, CGRP- and NKA-positive nerve fibers were detected. Particularly the large nerve fibers contained CR. VIP-positive fibers occurred especially around hair follicles and sweat glands. CGRP-positive nerve fibers were located close to the epidermal basal membrane, in the wall of blood vessels, and to a lesser extent around hair follicles. Immunoreactivity for SP and NKA in the dermis was observed predominantly in the papillary layer near the epidermal basal membrane. All neuropeptides tested in this study were also detected in the nerve fibers of the subcutis. Most of them were CGRP- and VIP-positive. They occurred in association with sweat glands and large arteries. NPY-positive nerve fibers are predominant in the wall of arteries, arterioles and veins. Nerve fibers containing NKA and SP were less common and identified only in the walls of large arteries in deeper dermal layers. In double-staining experiments, the NADPH-d reaction and reactivity to tubulin revealed a partial co-localization in nerve fibers, blood vessel walls, around glands and ganglionic cells. VIP-positive fibers were more common in the face skin than in the forearm. However, in forearm we detected more NPY-, CGRP-, NKA- and SP-positive nerve fibers than in face skin. These findings are important for future studies on skin disorders, such as sensory neuropathies, inflammatory reactions or allergic responses of human skin.
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PMID:Immunohistochemical detection of human skin nerve fibers. 938 13

The neurochemical composition of nerve fibres and cell bodies in the myenteric plexus of the proventriculus, stomach and small and large intestines of the golden hamster was investigated by using immunohistochemical and histochemical techniques. In addition, the procedures for localising nitric-oxide-utilising neurones by histochemical (NADPH-diaphorase) and immunohistochemical (nitric oxide synthase) methods were compared. The co-localisation of vasoactive intestinal polypeptide and nitric oxide synthase in the myenteric plexus of all regions of the gut was also assessed. The results demonstrated the presence of nerve fibres and nerve cell bodies immunoreactive to protein gene product, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide, tyrosine hydroxylase, 5-hydroxytryptamine and nitric oxide synthase in all regions of the gastrointestinal tract examined. The pattern of distribution of immunoreactive nerve fibres and nerve cell bodies containing the above markers was found to vary in different regions of the gut. Myenteric neurones and nerve fibres containing immunoreactivity to nitric oxide synthase and NADPH-diaphorase reactivity, however, were shown to have an identical distribution throughout the gut. In contrast to some studies on the guinea-pig and rat, the co-existence of vasoactive intestinal polypeptide and nitric oxide synthase was seen in only a small population of myenteric neurones.
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PMID:A neurochemical characterisation of the golden hamster myenteric plexus. 947 95

The innervation of the musculature in the ferret stomach, ileum, colon and urinary bladder was investigated using immunohistochemistry in noncolchicin-treated tissues. In the gastrointestinal tract two main subpopulations of myenteric neurones were found: cholinergic neurones expressing choline acetyltransferase (ChAT), which made up 68, 67 and 67% of the neurones in the stomach, ileum and colon, respectively, and nitrergic neurones containing nitric oxide synthase and NADPH-diaphorase (stomach: 23%, ileum: 21%, colon: 26%). In the stomach, cholinergic neurones expressed substance P (SP, 2% of all neurones), dopamine-beta-hydroxylase (DBH, 19%) but not tyrosine hydroxylase (TH) or vasoactive intestinal polypeptide (VIP), while nitrergic neurones contained VIP and neuropeptide Y (NPY). TH- but not DBH-immunoreactivity was observed in 4% of gastric neurones. Intense immunoreactivity in the musculature suggests that part of ChAT/SP- and NOS/NPY/VIP-positive neurones function as motorneurones. In the ileum, a high number (32%) of DBH-positive neurones was demonstrated. About half of the SP-positive neurones in the ileum also contained calcitonin gene-related peptide (CGRP). In the urinary bladder, only few intramural ganglia were observed. The smooth muscle was densely innervated by ChAT, NPY and DBH immunoreactive fibres. The data showed that the innervation of the ferret viscera exhibited similarities but also differences as compared with other mammalian species. Some of the chemical coding of myenteric neurones is remarkably similar to that observed in other mammals.
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PMID:Presence of putative neurotransmitters in the myenteric plexus of the gastrointestinal tract and in the musculature of the urinary bladder of the ferret. 950 49

Morphological changes in developing human gustatory papillae during the 6th to the 23rd postovulatory week have been studied. The general innervation pattern of taste papillae and taste bud primordia was revealed immunohistochemically using antibodies against protein gene product 9.5 (PGP9.5), neurofilament H (NFH), neurofilament L (NFL), neurone-specific enolase (NSE), and tubulin. The autonomic and somatosensory nerve supply has been investigated using antibodies against substance P (SP), calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), neuropeptide Y (NPY), the neuronal form of nitric oxide synthase (n-NOS), and, enzyme histochemically, NADPH-diaphorase. Nerve fibers approach the basal membrane of the lingual epithelium around the 7th postovulatory week and invade the epithelium of papilla-like structures at the 8th week, but some also penetrate the basal membrane of the non-papillary epithelium. They are in close contact with slender epithelial cells that are considered to be the taste bud's progenitor cells. Early human taste buds situated at the anterior part of the tongue do not necessarily require a dermal (later fungiform) papilla. The NADPH-diaphorase reaction revealed positive results in dermal nerve fibers, but the immunohistochemical reaction against n-NOS was negative. Immunohistochemical detection of neuropeptides and vasoactive substances rendered negative results for developmental stages of 7-18 postovulatory weeks. By the 18th week, only SP was detected in dermal papillae, but not in the vicinity of taste buds' primordia. Thus, autonomic and somatosensory nerves seem not to play a key role in formation and maintenance of early human taste buds.
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PMID:Innervation of developing human taste buds. An immunohistochemical study. 954 77

The neurochemical coding of neurones located in ganglia of the nerve trunk accompanying the chicken ureter was analysed and quantified using NADPH-diaphorase reactivity and immunohistochemistry against tyrosine hydroxylase (TH), nitric oxide synthase (NOS), calbindin (CAL), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and calcitonin gene-related peptide (CGRP) in untreated or colchicine-treated preparation. Almost all neurones were either positive for TH (38%) or for SOM (60%). Only 4% of the neurones were both TH- and SOM-positive and 3% of the neurones exhibited neither TH nor SOM immunoreactivity. The relative numbers of NPY-, NOS-, CAL- and VIP-positive neurones were 57%, 28%, 14% and 7%, respectively. No SP- or CGRP-positive neurones were observed. All NADPH-diaphorase-positive neurones expressed NOS immunoreactivity. Only in some TH-positive neurones was NPY and/or NOS found. Four major subpopulations were found in the ureteric ganglia. The SOM-positive neurones were subdivided into SOM/NPY/NOS- (28% of all neurones), SOM/NPY- (18%) and SOM/CAL/NPY-positive neurones (14%). A subpopulation of these peptid- ergic neurones also contained VIP. About 35% of the neurones contained TH only. Neurones of all subpopulations (72% of the neurones), except most of the CAL-positive neurones, were encircled by dense plexus of varicose SP/CGRP-positive, presumably sensory nerve fibres. Dense plexus of VIP-positive fibres were observed around 89% of the neurones. The chemical coding of the neuronal subpopulations identified in the ganglia accompanying the chicken ureter resembled that observed in the ganglia of Remak's nerve but was remarkably different from that of the autonomic neurones described in mammalian species.
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PMID:Neuronal subpopulations in autonomic ganglia associated with the chicken ureter: an immunohistochemical study. 958 4

We examined the role of K+ channels in the endothelium-dependent relaxation which is resistant to nitric oxide (NO) synthase inhibition in porcine coronary artery. In the presence of 0.2 mM NG-nitro-L-arginine (L-NNA), a potent inhibitor of NO synthase, 10 nM substance P (SP) added to 9,11-dideoxy-11alpha,9alpha-epoxymethano-prostaglandin F2alpha (U46619) contractures elicited a relaxation. The L-NNA-resistant relaxation induced by SP was strongly inhibited by 5 mM tetrabutylammonium chloride (TBA), a non-specific inhibitor of K+ channels. Interestingly, 4-aminopyridine (4-AP, 1 mM), a relatively specific inhibitor of voltage-sensitive K+ channels, shortened the duration of SP response, but it had no effect on the peak of SP response. Although 4-AP has also been shown to inhibit Ca2+-activated K+ channels, the shortening effect of 4-AP in SP response was observed in the presence of 1 microM apamin, an inhibitor of small conductance Ca2+-activated K+ channels, or 100 nM charybdotoxin, and inhibitor of large conductance Ca2+-activated K+ channels. Moreover, although SP stimulates both L-NNA-resistant relaxation and endothelium-derived NO-dependent relaxation (EDNO) in porcine coronary arteries, a low concentration of 4-AP (1 mM) affected only the L-NNA-resistant response, but not the EDNO response. These are the first results to show that the L-NNA-resistant relaxation induced by SP, probably, endothelium-derived hyperpolarizing factor(s) (EDHF) response, is dependent on voltage-dependent K+ channels in porcine coronary artery.
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PMID:The endothelium-dependent, substance P relaxation of porcine coronary arteries resistant to nitric oxide synthesis inhibition is partially mediated by 4-aminopyridine-sensitive voltage-dependent K+ channels. 958 20

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, through the formation of cGMP and the subsequent release of methionine enkephalin and leucine enkephalin in the newborn pig. In separate studies, these opioids also were observed to elicit NO-dependent pial artery dilation, whereas light/dye endothelial injury reduced hypoxic pial dilation. The current study was designed to investigate the role of the endothelial isoform of NO synthase in hypoxic pial dilation, associated opioid release, and opioid dilation in piglets equipped with a closed cranial window. N-iminoethyl-L-ornithine (L-NIO) (10(-6) mol/L), an antagonist that may have greater endothelial NO synthase inhibitory selectivity, had no effect on dilation elicited by hypoxia (PO2 approximately 35 mm Hg) (24 +/- 2 versus 24 +/- 2% in the absence and presence of L-NIO, respectively, n = 8). Hypoxic dilation was accompanied by increased CSF cGMP, which also was unchanged in the presence of L-NIO (394 +/- 19 and 776 +/- 63 versus 323 +/- 13 and 739 +/- 25 fmol/mL for control and hypoxia in the absence and presence of L-NIO, respectively, n = 6). Additionally, hypoxic pial dilation was associated with increased CSF methionine enkephalin, which also was unchanged in the presence of L-NIO (992 +/- 73 and 2469 +/- 197 versus 984 +/- 18 and 2275 +/- 185 pg/mL, respectively, n = 6). In contrast, methionine enkephalin-induced dilation was blocked by L-NIO (6 +/- 1, 10 +/- 1, and 16 +/- 1 versus 1 +/- 1, 1 +/- 1, and 2 +/- 1% for 10(-10), 10(-8), 10(-6) mol/L methionine enkephalin, respectively, before and after L-NIO, n = 8). Substance P-induced pial dilation was blunted by L-NIO, whereas responses to sodium nitroprusside and N-methyl-D-aspartate were unchanged. These data indicate that endothelial NO synthase contributes to opioid-induced pial artery dilation but not hypoxia-induced dilation. Additionally, these data suggest that neuronally derived NO contributes to hypoxic pial dilation.
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PMID:Role of endothelial nitric oxide synthase in hypoxia-induced pial artery dilation. 959 45

1. The possible contribution of the nonadrenergic noncholinergic (NANC) transmitters nitric oxide (NO) and substance P (SP) to the contractility of guinea pig isolated ileum was studied by the responses of the longitudinal muscle to electrical field stimulation (0.8 msec, 40 V, 1-20 Hz, 20 sec) of the intrinsic nerves and by the presence and distribution of NADPH-diaphorase- and SP-positive nerve structures in the myenteric plexus. 2. The electrically elicited, tetrodotoxin (0.3 microM)-sensitive responses, in the presence of phentolamine (5 microM), propranol (5 microM), and atropine (3 microM) consisted of relaxation, followed by twitch and tonic contraction on which phasic contractions were superimposed. 3. NG-nitro-L-arginine (L-NNA; 0.1 mM or 0.5 mM), an inhibitor of NO synthesis abolished the relaxation. L-arginine (0.1 mM), a substrate for NO synthesis, but not D-arginine, restored it. L-NNA concentration dependently increased the twitch and tonic contractions. Sodium nitroprusside (1 microM or 10 (M), an exogenous donor of NO, was without effect on the electrically evoked responses. 4. AP 13.2 ACOH (AP; 0.1 microM or 10 microM), a blocker of SP receptors, frequency dependently inhibited or even prevented the twitch and tonic contractions. AP concentration-dependently increased the relaxation or reversed the responses to electrical stimulation into a deep relaxation. 5. The concentration-response curve for SP (1 nM-0.1 microM) was shifted to the right by AP, the EC50 values being 5.2 +/- 0.4 nM and 88.0 +/- 3.0 nM, respectively. The effects of SP were not altered by L-NNA (0.1 mM). 6. These findings, supported by morphological data about distribution of NADPH-diaphorase-positive nerve cell bodies and processes and SP-positive varicose fibers, suggest the contribution of NO and SP to NANC transmission. It appears that NO inhibits prejunctionally the SP transmission whereas SP counteracts the NO effect at the postjunctional level.
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PMID:Contribution of nitric oxide and substance P to nonadrenergic, noncholinergic transmission in the guinea pig ileum. 959 87

Gastric adaptive relaxation is a vago-vagal reflex, probably involving the site of interface of vagal afferents and efferents in the dorsal vagal complex of the medulla. Previous studies have shown that both substance P and nitric oxide in the dorsal vagal complex decrease intragastric pressure. The purpose of this study is, firstly, to localize NK1 tachykinin receptor immunoreactive (ir) staining in the dorsal vagal complex and, secondly, to determine its anatomical relationship to nitrergic cells in the dorsal motor nucleus of the vagus. Sections were stained by avidin-biotin immunocytochemistry using antiserum to NK1 receptor alone or combined with NADPH-diaphorase histochemistry. In the nucleus tractus solitarius, NK1 receptor-ir varicosities were moderately dense in the medial subnucleus, but sparse in the centralis and gelatinosus subnuclei. In the dorsal motor nucleus of the vagus, NK1 receptor-ir staining in cell bodies and fibers was present throughout, with a markedly dense varicose fiber and cell body staining in a lateral column of the rostral portion of the nucleus. NADPH-diaphorase staining is most marked in cell bodies in the same region of the dorsal motor nucleus of the vagus. In dual-stained sections, there was complete overlap of NADPH-diaphorase and NK1 receptor-ir stain; however, the markers were very rarely colocalized within the same vagal motor neurons. Ipsilateral vagotomy almost completely abolished NK1r-ir staining in vagal motor neurons. We conclude that, in the dorsal motor nucleus of the vagus, NK1 receptor is synthesized by a population of vagal motor neurons which are in close anatomical proximity to, but separate from, nitrergic neurons. Based on these observations, substance P-mediated gastric relaxation in this region is unlikely to be via activation of nitrergic vagal preganglionic neurons. In the nucleus tractus solitarius, the NK1 receptor and NADPH-diaphorase stain are not codistributed in subnuclei mediating gastric and esophageal control. Therefore, substance P and nitric oxide may mediate their respective gastrointestinal effects via separate afferent pathways.
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PMID:Immunocytochemical distribution of neurokinin 1 receptor in rat dorsal vagal complex. 966 58

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