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)

To elucidate the regulation mechanism of adrenomedullin (AM) production in blood vessels, we examined the effects of 30 substances on AM production in cultured rat vascular smooth muscle cells (VSMCs). Forskolin and 8-bromo-cAMP suppressed production and gene transcription of AM. Since VSMC expresses AM receptors coupled with adenylate cyclase, AM production may be regulated by intracellular cAMP concentration. Thrombin, vasoactive intestinal polypeptide and interferon-gamma also inhibited AM production, while angiotensin II, endothelin-1, bradykinin, substance P, adrenaline, phorbol ester and fetal calf serum stimulated AM production in VSMC. These results suggest that AM production is regulated by a variety of substances, indicating complex systems regulating AM production.
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PMID:Effects of vasoactive substances and cAMP related compounds on adrenomedullin production in cultured vascular smooth muscle cells. 764 78

This study describes the localization of endothelin-1-, vasopressin- and substance P-like immunoreactivity in a subpopulation of endothelial cells of the basilar and posterior communicating arteries of the (i) normal rabbit brains and (ii) rabbit brains perfused with a perfluorocarbon emulsion (PFC). Following perfusion with the PFC at increased flow the endothelial cell ultrastructure appeared normal, although there was a decrease of immunoreactivity to these peptides. This suggests that these peptides may be involved in endothelial control of blood flow in cerebral vessels.
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PMID:Electron-immunocytochemistry of peptides in endothelial cells of rabbit cerebral vessels following perfusion with a perfluorocarbon emulsion. 768 5

The contractile response of cultured Ito cells to endothelin-1 and substance P was examined. Ito cells were obtained from rat liver by perfusion with collagenase, followed by separation through centrifugal elutriation, and were cultured for 24 hr. The area of the Ito cells was measured after treatment with endothelin-1 or substance P at various concentrations in the culture medium. The area of the cells decreased dose dependently after treatment with endothelin-1 or substance P. The area of Ito cells before addition of interleukin-1 or substance P was defined as 100%. The area of the cells after treatment with endothelin-1 or substance P medium was expressed as the percentage against the area before treatment with endothelin-1 or substance P. The percentage in area after treatment with 200 nmol/L endothelin-1 was as follows: 81% +/- 13% at 30 min, 77% +/- 15% at 60 min, 87% +/- 15% at 120 min and 99% +/- 18% at 180 min. The maximal decrease in area occurred at 60 min after treatment. The percentage values for 200 nmol/L substance P were as follows: 88% +/- 15% at 10 min, 95% +/- 17% at 30 min and 101% +/- 17% at 60 min. The maximal decrease in area was noted at 10 min. Thus Ito cells contracted in response to treatment with endothelin-1 or substance P. The mode of the extent and onset of the contraction was different for the two peptides. These findings suggest that Ito cells are involved in the regulation of the hepatic sinusoidal microcirculation.
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PMID:Ito cell contraction in response to endothelin-1 and substance P. 769 8

The innervation and vasomotor responses to several vasoactive agents of guinea pig epicardial coronary veins were investigated by means of immunohistochemical, histochemical, ultrastructural and in vitro pharmacological techniques. The use of an antiserum to the general neuronal marker protein gene product 9.5 revealed that coronary veins are supplied by a network of fine varicose nerve fibres in the adventitia. The majority of the nerve fibres possessed neuropeptide Y (NPY) and tyrosine hydroxylase immunoreactivity. Only a few nerve fibres displayed substance P, neuropeptide K (NK) and calcitonin gene-related peptide (CGRP) immunoreactivity. In double stained preparations substance P immunoreactivity was co-localized with NK and CGRP in the same nerve fibres. Nerve fibres containing vasoactive intestinal peptide (VIP) immunoreactivity or acetylcholinesterase activity were not detected. Endothelin immunoreactivity was also found in the vein endothelial cells. Ultrastructural studies revealed the presence of axon varicosities at the adventitial-medial border. In vitro pharmacological studies showed that endothelin-1 and -2 elicited a significant contractile response of epicardial vein segments. Noradrenaline, NPY, serotonin and uridine 5'-triphosphate induced only a relatively weak contractile response in the vein segments. Although vasodilatory responses were difficult to examine in these preparations, it was found that substance P, CGRP and VIP elicited a relaxation of the vein segments. These results indicate that guinea pig epicardial coronary veins are innervated by several nerve populations, however, the control of vasomotor tone of coronary veins appears to be predominantly regulated by 'non-neuronal' vasoactive agents such as endothelin and 5-HT.
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PMID:The innervation of guinea pig epicardial coronary veins: immunohistochemistry, ultrastructure and vasomotility. 791 47

1. The vascular reactivity of resistance arteries isolated from gluteal skin biopsies and veins isolated from forearms of subjects fed marine oils were examined. 2. Twenty seven healthy adult males were randomly allocated to one of two different treatment groups. The first group received maxEPA (eicosapentaenoic acid 0.178 g g-1; docosahexaenoic acid 0.116 g g-1) capsules 10 g per day for 28 days while the second group received an equivalent amount of mixed oil placebo capsules. Biopsies were performed on day 29 (13 for gluteal sections; 14 for forearm vein biopsies). Subcutaneous arteries and veins were mounted in myographs and standard organ baths, respectively. 3. The internal diameter of the subcutaneous arteries at a calculated transmural pressure of 100 mmHg averaged 183.7 +/- 10.3 microns in the maxEPA group and 182.6 +/- 19.8 microns in the placebo controls. Arteries from subjects on maxEPA demonstrated increased sensitivity to angiotensin II (maxEPA vs placebo: -log EC50 (M) -8.36 +/- 0.18 vs -7.91 +/- 0.14) but not to noradrenaline or 5-hydroxytryptamine. Concentration-response curves to acetylcholine, substance P and sodium nitroprusside obtained for noradrenaline precontracted vessels were unaltered with marine oil treatment as was the concentration-response curve to calcium in K(+)-depolarized vessels. 4. Vein internal diameter at a calculated transmural pressure of 20 mmHg averaged 3.06 +/- 0.23 mm in the maxEPA group and 2.96 +/- 0.89 in the placebo group. Responses to noradrenaline, 5-hydroxytryptamine, angiotensin II and endothelin-1 were obtained in the absence and presence of indomethacin (1 microM) in veins from both maxEPA and placebo-treated subjects. Neither dietary supplementation with marine oils nor indomethacin had any effect on the responses obtained to these agonists.5. The major finding of the present study was that in general, maxEPA supplementation did not affect responses to various vasoactive substances on isolated subcutaneous arteries or forearm veins. An exception was the observation of an enhanced response to angiotensin II in subcutaneous resistance arteries studied in vitro. This effect was selective for angiotensin II and was not apparent in veins isolated from the forearm.
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PMID:Effects of dietary marine oil supplementation on reactivity of human buttock subcutaneous arteries and forearm veins in vitro. 807 74

We investigated the possibility that cultured corneal endothelial cells express receptors that are coupled to the phosphoinositide cycle/intracellular Ca2+ signaling pathway. Agonist-stimulated changes in intracellular calcium ([Ca2+]i) in single bovine and human corneal endothelial cells (BCEC and HCEC, respectively) derived from confluent cultures were measured by microspectrofluorimetry using the Ca(2+)-sensitive probe, fura-2. Total inositol phosphates accumulated during a 30 min incubation in the presence or absence of agonists was determined in Li+ containing medium with cells pre-labelled for 48 hrs with 10 microCi/ml 3H-myoinositol. Histamine (HA), ADP and ATP induced a rapid increase in [Ca2+]i. Subsequently, [Ca2+]i decreased to either a stable, agonist-dependent sustained elevation, or fell back to baseline to begin oscillatory fluctuations. The initial rise in [Ca2+]i was insensitive to removal of extracellular calcium (Ca2+o), whereas the stable elevations in [Ca2+]i and the [Ca2+]i oscillations required Ca2+o. In contrast, bradykinin (BK) and endothelin-1 (ET-1) elicited an initial rise in [Ca2+]i that returned to prestimulatory levels within 2 min despite the continued presence of agonist. The Ca(2+)-mobilizing agonists carbachol, phenylephrine, adenosine and substance P were all ineffective in elevating [Ca2+]i. Histamine-induced Ca2+ mobilization was inhibited by the H1-receptor antagonist triprolidine, but triprolidine had no effect on either BK or ATP stimulation of Ca2+ mobilization. In BCEC, 100 microM HA significantly increased total inositol phosphate accumulation (18.8-fold over unstimulated controls) and was 90% inhibited by 0.5 microM triprolidine. BK and ATP also significantly increased formation of inositol phosphates in BCEC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Agonist-induced Ca2+ mobilization in cultured bovine and human corneal endothelial cells. 810 Apr 93

Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.
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PMID:Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells. 836 38

The effects of endothelin-1 (ET-1) on protein synthesis and phosphoinositide (PI) hydrolysis were investigated in ventricular myocytes isolated by collagenase digestion of adult rat hearts. The maximum stimulation of protein synthesis by ET-1 was about 35% and the EC50 value was about 0.3 nM. The stimulation was exerted at the translational stage since it was insensitive to inhibition by actinomycin D. The maximum stimulation of PI hydrolysis by ET-1 as measured by the formation of [3H]inositol phosphates was about 11-fold and the EC50 value was about 0.7 nM. The ET-1 analogue sarafotoxin-6b stimulated protein synthesis by a maximum of 27% and stimulated PI hydrolysis about 8- to 9-fold. The EC50 values were 1.6 nM and 0.6 nM, respectively. Other endothelins stimulated protein synthesis and PI hydrolysis in the following order of potency: ET-1 approximately ET-2 > ET-3. This order of potency suggests that the stimulation of both protein synthesis and PI hydrolysis is mediated through the ETA receptor. Although both angiotensin II and [Arg]vasopressin stimulated PI hydrolysis significantly, the stimulation was less than 60%, i.e., much less than the stimulation by ET-1 and its analogues. Neither insulin nor substance P stimulated PI hydrolysis. Stimulation of protein synthesis by ET-1 and its analogues correlated strongly with the stimulation of PI hydrolysis and we suggest that the stimulation of protein synthesis may be dependent on the stimulation of PI hydrolysis. We hypothesize that the mechanism may involve a protein kinase C-mediated increase in intracellular pH.
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PMID:Stimulation of adult rat ventricular myocyte protein synthesis and phosphoinositide hydrolysis by the endothelins. 838 85

We investigated the effect of endothelin-1 on relaxation responses induced by vasodilator substances in canine middle cerebral arteries to better understand regulation of cerebrovascular tone and its potential impact on mechanism of cerebral vasospasm. Endothelin-1 elicited concentration-dependent contractions in helical strips of canine cerebral arteries (EC50; 4.62 x 10(-9) M). Pretreatment with 10(-9) M endothelin-1 significantly reduced endothelium-dependent relaxation elicited by substance P and endothelium-independent relaxations by nitroglycerin, prostaglandin I2, and KCl. Although endothelin-1 in a lower concentration (10(-10) M) did not affect these endothelium-independent relaxations, it did inhibit endothelium-dependent relaxation caused by substance P. A low concentration (10(-10) M) of endothelin-1 also significantly reduced endothelium-dependent relaxation of canine mesenteric arteries induced by acetylcholine. Other vasoconstrictor peptides such as angiotensin-II and vasopressin did not inhibit endothelium-dependent and -independent relaxations. These results indicate that endothelin-1 not only produces cerebral vasoconstriction but also interferes with vasodilator mechanisms and that endothelium-dependent vasodilation is more sensitive to the inhibitory effect of endothelin-1 than endothelium-independent vasodiltion.
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PMID:Suppression of cerebral vasodilation with endothelin-1. 853 97

1. The relative contribution of ETA and ETB receptors in the response of rat skin to endothelins was investigated by use of the selective ETB agonist IRL-1620 and the selective ETA antagonist BQ-123. 2. Binding data suggest the presence of ETA and ETB receptors as preincubation with [Ala3,11,18Nle7]-endothelin-1 reduced ET-1 binding by approximately 40%. 3. Intradermal injection of endothelin-1 (ET-1, 1-10 pmol/site) and ET-3 (3-100 pmol/site) induced a dose-dependent decrease in local blood flow assessed by 133Xe clearance at test sites in rat skin. 4. The endothelin analogue [Ala3,11,18Nle7]-ET-1 (30-1000 pmol/site) induced significant vasoconstriction (P < 0.05) at the highest doses used and the selective ETB receptor agonist, IRL-1620 [Suc[Glu9,Ala11,15] endothelin (8-21)], (0.01-100 pmol/site) acted in a potent manner to induce a significant (P < 0.01) dose-dependent decrease in 133Xe clearance. 5. Co-injection with the selective ETA receptor antagonist, BQ-123 (1 nmol/site), completely abolished the vasoconstriction to ET-1 and partially to ET-3, but had no effect on IRL-1620-induced vasoconstriction. In addition, IRL-1620 responses were not altered at sites treated with submaximal doses of a nitric oxide synthase inhibitor or a prostaglandin synthase inhibitor. 6. ET-1 and IRL-1620 (100 fmol-1 pmol/site) did not induce oedema formation as measured by [125I]-albumin accumulation in the presence or absence of the vasodilator, calcitonin gene-related peptide (CGRP). ET-1 (1-3 pmol/site) inhibited substance P-induced oedema formation and this effect,suggested to be secondary to a vasoconstrictor effect, was significantly reversed by BQ-123 (1 nmol/site).7. The findings in this study indicate that there are ETA and ETB receptors in rat skin and agents which activate either receptor act to mediate a decrease in cutaneous blood flow, but have no effect on increased microvascular permeability.
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PMID:Evidence for ETA and ETB receptors in rat skin and an investigation of their function in the cutaneous microvasculature. 854 85


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