UNIPROT:P20366 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

The characteristics of arteriolar myogenic responses of female rats have not been investigated. Thus experiments were conducted on isolated gracilis muscle arterioles (approximately 55 microm diameter) of four groups of 12-wk-old rats: male rats, female rats, ovariectomized female rats with no estrogen replacement (OV), and ovariectomized female rats with estrogen replacement (OV + E2, 50 microg/kg s.c. injection of 17beta-estradiol benzoate every 48 h). Diameter changes in response to increases in perfusion pressure from 20 to 140 mmHg and to various concentrations of substance P (SP, 10(-9)-5 x 10(-8) M) and sodium nitroprusside (SNP, 10(-8)-10(-6) M) were measured before and after administration of N(omega)-nitro-L-arginine (L-NNA, 10(-4) M), an inhibitor of NO synthase. Arteriolar diameters of male and OV female rats were significantly less at 60-140 mmHg pressure than those of normal female and OV + E2 female rats (at 80 mmHg, 45.4 +/- 1.8 and 43.1 +/- 2.2 vs. 58.4 +/- 1.6 and 57.3 +/- 1.3%). L-NNA elicited a significantly greater downward shift of pressure-diameter curves in arterioles of normal female and OV + E2 female rats than in arterioles of male and OV female rats (28.6 +/- 4.6 and 30.6 +/- 4.7 vs. 13.2 +/- 0.9 and 10.4 +/- 2.6%). Dilations of arterioles from normal female and OV +/- E2 female rats to SP were significantly greater (by 50-60%) than those from male and OV female rats (20.8 +/- 1.8 and 22.3 +/- 1.9 vs. 13.8 +/- 1.4 and 13.8 +/- 0.6% at 10(-8) M). L-NNA did not affect dilations to SNP but significantly reduced the dilation of arterioles in all groups to SP, more so in arterioles of male and OV female rats than in arterioles of the other two groups. We conclude that pressure-induced myogenic constriction of arterioles of female rats is less pronounced than that of male rats; this is, most likely, due to the enhanced release and/or activity of NO related to the presence of estrogen.
...
PMID:Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO. 913 66

In this work, we have studied the effects and the possible cellular mechanism of Substance P (SP) on corticosteroid secretion by the adrenal gland of the urodele crested newt, Triturus carnifex. Adrenals were in vitro superfused with SP, prostaglandin E2 (PGE2), nitric oxide (NO) donor, cyclic GMP (cGMP) analogue, and inhibitors of phospholipase A1, phospholipase A2 (PLA2), phospholipase C, adenylate cyclase (AC), cyclooxygenase (COX), NO synthase (NOS), and soluble guanylate cyclase (sGC). PGE2, corticosterone, and aldosterone release and NOS activity were determined. SP, PGE2, NO donor, and cGMP analogue increased corticosterone and aldosterone; SP and PGE2 increased NOS, and SP increased PGE2. PLA2, AC, COX, NOS, and sGC inhibitors counteracted SP and PGE2 effects, except for PLA2, which did not affect PGE2. These results suggest that SP exhibits a stimulatory role on the corticosteroidogenesis of T. carnifex adrenal gland. In particular SP enhances PLA2 activity, increasing PGE2; this prostaglandin affects AC, which, in turn, enhances NO, and the latter therefore affects sGC, with the consequent corticosteroidogenesis increase.
...
PMID:Cellular mechanism of substance P in the regulation of corticosteroid secretion by newt adrenal gland. 914 46

We reported previously that NO is responsible for the angiogenesis produced by endothelium-dependent vasodilating peptides. To investigate the mechanisms by which NO controls angiogenesis, NO was assessed for the ability to affect cell proliferation and upregulation of urokinase-type plasminogen activator (uPA) induced by basic fibroblast growth factor (bFGF) when added exogenously to or when produced endogenously by coronary venular endothelial cells (CVECs). The treatment of the cells with the NO donor sodium nitroprusside (NaNp) induced uPA upregulation and cell proliferation, which were prevented by anti-bFGF antibodies. Similarly, the NO-dependent mitogenic activity of the vasodilating peptide substance P (SP) was blocked by anti-bFGF antibodies, thus implicating endogenous bFGF in the NO-induced response. NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase-polymerase chain reaction of bFGF mRNA. SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N omega-monomethyl-L-arginine. We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP. This signaling paradigm may provide an important link between shear rate, NO, bFGF, and coronary angiogenesis.
...
PMID:Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF. 916 87

37 complete frontal and horizontal series of rat brain were studied to compare the distribution of choline acetyltransferase- (ChAT), tyrosine hydroxylase- (TH), substance P- (SP), calbindin D- (Calb) and NADPH-diaphorase (NADPH-d)-positive cells within the cytoarchitectonic borders of the latero-dorsal tegmental nucleus (L-D) and its neighbourhood. We found the same distribution, number and morphology of NADPH-d-positive cells and ChAT-positive cells. Rostrally, there are no borders between NADPH-d-positive cells of L-D and NADPH-d-positive cells of the lateral part of the dorsal raphe nucleus. Only a few TH-positive cells are intermingled with ChAT/NADPH-d-positive cells at the lateral border of L-D. TH-positive cells are larger or the same size as cholinergic neutrons. Locus coeruleus and its rostral part is full of TH-positive cells and their fibres run ventromedially towards L-D. Barrington's nucleus appears in double staining (ChAT and TH or NADPH-d and TH) as an empty area bordered by ChAT- or NADPH-d-positive cells of L-D and TH-positive fibres of the locus coeruleus. Some of these fibres run through the Barrington's nucleus. The shape and size of SP-positive neurons is the same as ChAT- and NADPH-d-positive neurons. SP-positive neurons are sparsely distributed in all parts of L-D, but there are only a few SP-positive cells in its medial part. About 50% of the ChAT- and NADPH-d-positive cells are also SP-positive. Results are expressed by figures in three representative frontal sections and one horizontal section through the dorsal mesopontine tegmentum.
...
PMID:The dorsal tegmentum of the pontomesencephalic junction of the rat--immunohistochemistry (choline acetyltransferase, tyrosine hydroxylase, substance P) and NADPH-diaphorase histochemistry in frontal and horizontal sections. 917 35

In this study, enteric nervous system (ENS) of the fetal intestinal grafts was examined histopathologically. Forty-four rat fetal small intestines were transplanted syngenetically into the subcutaneous region of adult rats without vascular anastomosis. Thirty-two grafts survived. They were removed 2, 4, 6, and 8 weeks after transplantation and examined using (1) H&E staining, (2) AChE and NADPH-diaphorase histochemistry, and (3) protein gene product 9.5, S-100 protein, glial fibrillary acidic protein, tyrosine hydroxylase, nerve growth factor receptor, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal peptide, somatostatin, and substance P immunohistochemistry. The grafts were compared with the intestines of 2-, 4-, 6- and 8-week-old control rats. ENS of the grafts was different from the controls as follows: (1) tyrosine hydroxylase and neuropeptide Y were markedly reduced but present, suggesting that the extrinsic innervation was present; (2) nitric oxide-producing neurons were well preserved in grafts; (3) hyperganglionosis in the myenteric plexus was seen in 6- and 8-week grafts; (4) AChE activity was increased in the circular muscle and in the lamina propria, (5) S-100 was increased in the lamina propria in 6- and 8-week grafts, (6) calcitonin gene-related peptide was increased in 6- and 8-week grafts, (7) nerve fibers in the muscle layers ran irregularly and disorderly, and (8) hypertrophy of smooth muscle layers. Our data show that although extrinsic as well as intrinsic innervation is present in the fetal intestinal grafts, there is hyperinnervation of the intrinsic nervous system and reduced innervation of the extrinsic ENS. These morphological changes in the ENS of the fetal intestinal grafts may result in motility dysfunction.
...
PMID:Morphological changes in the enteric nervous system of the transplanted fetal rat intestine. 920 96

The effects of tetraethylammonium (TEA), a K+ channel antagonist, on vasodilator responses were investigated in the hindquarters vascular bed of the cat under constant-flow conditions. After administration of TEA in a total dose of 60 mg/kg into the hindquarters perfusion circuit, vasodilator responses to acetylcholine, bradykinin, and substance P were reduced, whereas vasodilator responses to the NO donors, diethylamine-NO complex, S-nitroso-N-acetylpenicillamine, and sodium nitroprusside, and to prostaglandin E1, albuterol, vasoactive intestinal polypeptide, isradipine, and levcromakalim were not altered. The inhibitory effect of TEA on responses to the endothelium-dependent vasodilators was reversible with time, and vasoconstrictor responses to norepinephrine, U-46619, angiotensin II, and BAY K 8644 were enhanced by the K+ channel antagonist. Although TEA had no sustained effect on baseline systemic arterial and hindquarters perfusion pressures, the NO synthase inhibitor, N omega-nitro-L-arginine methyl ester, increased these pressures in the presence of TEA. The results of the present investigation suggest that TEA attenuates vasodilator responses to acetylcholine, bradykinin, and substance P by inhibiting the release of endothelium-derived relaxing factor. These data suggest that the acetylcholine-, bradykinin-, and substance P-stimulated release of endothelium-derived relaxing factor may involve the opening of a TEA-sensitive K+ channel in the endothelium in the hindlimb vascular bed of the cat, but that a TEA-sensitive mechanism is not involved in the maintenance of baseline tone in this vascular bed.
...
PMID:Vasodilator responses to acetylcholine, bradykinin, and substance P are mediated by a TEA-sensitive mechanism. 924 80

Plasma extravasation from postcapillary venules is one of the earliest steps of inflammation. Substance P (SP) and bradykinin (BK) mediate extravasation and cause hypotension. The cell-surface enzyme neutral endopeptidase (NEP) inactivates both peptides. Thus, absence of NEP may predispose development of inflammation and hypotension. We examined these possibilities in mice in which the NEP gene was deleted by homologous recombination. There was widespread basal plasma extravasation in postcapillary venular endothelia in NEP-/- mice, which was reversed by recombinant NEP and antagonists of SP (NK1) and BK (B2) receptors. Mean arterial blood pressure was 20% lower in NEP-/- animals, but this was unaffected by reintroduction of recombinant NEP and the kinin receptor antagonists. The hypotension was also independent of nitric oxide (NO), because NEP-/- mice treated with a NO synthase inhibitor remained hypotensive relative to the wild type. Thus, NEP has important roles in regulating basal microvascular permeability by degrading SP and BK, and may regulate blood pressure set point through a mechanism that is independent of SP, BK and NO. The use of NEP antagonists as candidate drugs in cardiovascular disease is suggested by the blood pressure data reported herein.
...
PMID:The control of microvascular permeability and blood pressure by neutral endopeptidase. 925 83

The muscle and epithelial tissues of the gallbladder are regulated by a ganglionated plexus that lies within the wall of the organ. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical and physiological characteristics that are distinct from the myenteric and submucous plexuses of the enteric nervous system. Structurally, the ganglionated plexus of the guinea pig gallbladder is comprised of small clusters of neurons that are located in the outer wall of the organ, between the serosa and underlying smooth muscle. The ganglia are encapsulated by a shell of fibroblasts and a basal lamina, and are devoid of collagen. Gallbladder neurons are rather simple in structure, consisting of a soma, a few short dendritic processes and one or two long axons. Results reported here indicate that all gallbladder neurons are probably cholinergic since they all express immunoreactivity for choline acetyltransferase. The majority of these neurons also express substance P, neuropeptide Y, and somatostatin, and a small remaining population of neurons express vasoactive intestinal peptide (VIP) immunoreactivity and NADPH-diaphorase enzymatic activity. We report here that NADPH-diaphorase activity, nitric oxide synthase immunoreactivity, and VIP immunoreactivity are expressed by the same neurons in the gallbladder. Physiological studies indicate that the ganglia of the gallbladder are the site of action of the following neurohumoral inputs: 1) all neurons receive nicotinic input from vagal preganglionic fibers; 2) norepinephrine released from sympathetic postganglionic fibers acts presynaptically on vagal terminals within gallbladder ganglia to decrease the release of acetylcholine from vagal terminals; 3) substance P and calcitonin gene-related peptide, which are co-expressed in sensory fibers, cause prolonged depolarizations of gallbladder neurons that resemble slow EPSPs; and 4) cholecystokinin (CCK) acts presynaptically within gallbladder ganglia to increase the release of acetylcholine from vagal terminals. Results reported here indicate that hormonal CCK can readily access gallbladder ganglia, since there is no evidence for a blood-ganglionic barrier in the gallbladder. Taken together, these results indicate that gallbladder ganglia are not simple relay stations, but rather sites of complex modulatory interactions that ultimately influence the functions of muscle and epithelial cells in the organ.
...
PMID:Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia. 932 15

Because of the evidence that endogenous nitric oxide (NO) plays an essential role in the physiological regulation of gastrointestinal motility we have investigated, by use of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), the role of endogenous NO in the acute endotoxin-induced changes of gastrointestinal transit. Pre-treatment with E. coli endotoxin (100 micrograms kg-1, i.v.) induced a significant increase in the gastrointestinal transit of a charcoal suspension in anaesthetized rats. Previous administration of the NO synthase inhibitor, L-NAME (10 mg kg-1, i.v.) significantly prevented the effects of endotoxin. L-arginine (200 mg kg-1, i.v.) and the substance P antagonist [D-Pro2, D-Trp7,9]-substance P (SPA), significantly reversed the effects of L-NAME on gastrointestinal transit in rats treated with endotoxin. Pre-treatment with dexamethasone (5 mg kg-1, s.c., twice), an inhibitor of the expression of inducible NO synthase, did not affect the increase in the gastrointestinal transit through constitutive NO synthesis. The results suggest that constitutive nitric oxide is involved in the increase of gastrointestinal transit induced by endotoxin and that the reduction in transit induced by L-NAME in endotoxin-treated rats is mediated by endogenous tachykinins.
...
PMID:Nitric oxide modulates the acute increase of gastrointestinal transit induced by endotoxin in rats: a possible role for tachykinins. 936 8

1. We investigated the effect of acute inhalation of cigarette smoke on subsequent non-adrenergic, non-cholinergic (NANC) neural bronchoconstriction in anaesthetized guinea-pigs in vivo by use of pulmonary insufflation pressure (PIP) as an index of airway tone. The contribution of endogenous nitric oxide (NO) was investigated with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). The contribution of plasma exudation to the response was investigated with Evans blue dye as a plasma marker. 2. Inhalation of 50 tidal volumes of cigarette smoke or air had no significant effect on baseline PIP. In the presence of propranolol and atropine (1 mg kg(-1) each), electrical stimulation of the vagus nerves in animals given air 30 min previously induced a frequency-dependent increase in PIP above sham stimulated controls (16 fold increase at 2.5 Hz, 24 fold increase at 10 Hz). In contrast, in smoke-exposed animals, the increase in subsequent vagally-induced PIP was markedly less than in the air controls (90% less at 2.5 Hz, 76% less at 10 Hz). 3. L-NAME (10 mg kg[-1]), given 10 min before air or smoke, potentiated subsequent vagally-induced (2.5 Hz) NANC bronchoconstriction by 338% in smoke-exposed animals, but had no significant effect in air-exposed animals. The inactive enantiomer D-NAME (10 mg kg[-1]) had no effect, and the potentiation by L-NAME was partially reversed by the NO-precursor L-arginine (100 mg kg[-1]). Vagal stimulation did not affect the magnitude of vagally-induced bronchoconstriction 30 min later. 4. Cigarette smoke exposure reduced the magnitude of subsequent bronchoconstriction induced by neurokinin A (NKA) by 37% compared with the effect of NKA in air-exposed animals. L-NAME had no significant effect on the smoke-induced inhibition of NKA-induced bronchoconstriction. 5. Vagally-induced plasma exudation in the main bronchi was greater in smoke-exposed animals compared with air-exposed animals (120% greater at 2.5 Hz, 82% greater at 10 Hz). 6. We conclude that cigarette smoke-induced inhibition of subsequent NANC neurogenic bronchoconstriction is not associated with inhibition of airway plasma exudation and is mediated in part via exogenous smoke-derived NO, or another bronchoprotective molecule, and by endogenous NO.
...
PMID:Cigarette smoke-inhibition of neurogenic bronchoconstriction in guinea-pigs in vivo: involvement of exogenous and endogenous nitric oxide. 937 77

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>