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)

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

The aim of the present study was to evaluate the role of the endothelium in low pH-, capsaicin-, and prostacyclin (PGI2)-evoked release of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) from C-fibre afferents in the isolated, perfused guinea-pig heart. CGRP-LI release, and formation of the stable PGI2-metabolite 6-keto-PGF1 alpha, in response to moderate acidosis (pH 7, 6, but not 5) were significantly reduced after removal of endothelium using saponin (50 micrograms mL-1) perfusion. In contrast, the release of CGRP-LI evoked by capsaicin (10(-7) M) or PGI2 (10(-5) M) remained unchanged after removal of the endothelium. Saponin treatment did not influence the vasodilator action of CGRP, whereas the vasodilation evoked by substance P (SP) was abolished. It is concluded that CGRP release evoked by low pH, but not that evoked by capsaicin or exogenous PGI2, is partly endothelium dependent. Our data suggest that endothelially produced PGI2 is involved in low pH-evoked release of CGRP from capsaicin sensitive nerves in the heart.
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PMID:Attenuation of low pH-, but not capsaicin- or PGI2-evoked CGRP-release by endothelium removal using saponin. 861 22

1. Expression of prostacyclin receptor (IP receptor) mRNA was examined in various mouse organs, and the cells expressing IP receptor mRNA were identified by in situ hybridization studies. Co-localization of mRNA for the IP receptor with that for preprotachykinin A (PPTA), a precursor protein for substance P, with mRNA for the prostaglandin E receptor subtypes (EP1, EP3 and EP4), and with renin mRNA, was examined by double in situ hybridization studies in the dorsal root ganglion and kidney, respectively. 2. IP receptor mRNA was expressed in the thymus and spleen. Expression in the thymus was found exclusively in the medulla, where mature thymocytes expressed transcripts for the IP receptor. Expression in the spleen was found as scattered signals over the white pulp and as punctate signals in the red pulp. The former was found in splenic lymphocytes and the latter in megakaryocytes. 3. IP receptor mRNA was also expressed in the vascular tissues of various organs such as the aorta, coronary arteries, pulmonary arteries and the cerebral arteries, where its expression was confined to smooth muscle cells. No expression was found in veins. In the kidney, IP receptor mRNA was detected in the interlobular arteries and glomerular arterioles but not in the juxtaglomerular (JG) cells which were labelled with the renin mRNA probe. 4. IP receptor mRNA was expressed in about 40% of the neurones in the dorsal root ganglion. Both small- and large-sized neurones were labelled but no labelling was found in the glia. Expression of PPTA mRNA was found in about 30% of total neurones. About 70% of these neurones expressed IP receptor mRNA, and about half of the IP receptor-positive neurones expressed PPTA mRNA. In addition to IP mRNA, mRNAs for EP1, EP3 and EP4 receptors were expressed in about 30%, 50% and 20%, respectively, of the dorsal root ganglion neurones. About 25%, 41% and 24% of the IP receptor-positive neurons co-expressed the EP1, EP3 and EP4 receptor, respectively. 5. These results not only verified IP receptor expression in various cells and tissues known to be sensitive to prostacyclin, but also revealed its expression in other systems, which urges the study of the actions of prostacyclin in these tissues. They also indicated that the actions of prostacyclin on blood vessels and platelets are mediated by the same type of receptor. Absence of IP receptor mRNA in the JG cells suggests that the action of prostacyclin on renin release may be indirect.
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PMID:In situ hybridization studies of prostacyclin receptor mRNA expression in various mouse organs. 868 Jul 13

The effect of substance P (SP) on atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. Incubation of cells with SP led to a marked increase in ANP secretion, a response accompanied by increases in alpha-type protein kinase C (PKC) in the membranous cell fraction and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) formation and a small increase in adenosine 3',5'-cyclic monophosphate (cAMP) production. A role for PKC in SP-induced 6-keto-PGF1 alpha formation and ANP release was apparent insofar as the responses were suppressed by PKC inhibitors and in PKC-downregulated cells. Furthermore, SP-induced 6-keto-PGF1 alpha production was strongly correlated with SP-induced ANP secretion (r = 0.91, P < 0.0001, n = 27), suggesting a role for prostaglandins in SP-mediated ANP release. Supporting this, indomethacin abolished SP-induced ANP release, whereas PGE2, PGF2 alpha, and prostacyclin (PGI2) promoted ANP secretion in this system. Both the profile of SP-induced cAMP production and results obtained with prostaglandin antagonists suggest that a prostanoid FP receptor is at the basis of this response. Finally, both neurokinins A and B induced similar ANP responses, whereas cultured cells were found to contain mRNA transcripts coding for both neurokinin NK1 and NK3 receptor subtypes. Overall, these results suggest that SP induces ANP secretion in neonatal ventricular cardiomyocytes through a PKC- and prostaglandin-dependent signaling pathway.
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PMID:Stimulation of atrial natriuretic peptide release by neurokinins in neonatal rat ventricular cardiomyocytes. 878 Jan 88

1. The effect of pretreatment with bacterial endotoxin (LPS, 10 micrograms, i.v., 24 h) on the bradykinin B1 and B2 receptor-induced oedema in the rat paw, and the interaction of B1-mediated responses with other inflammatory mediators, was investigated. 2. Intraplantar (i.pl.) injection of the selective B1 agonist, des-Arg9-BK (DABK, 100 nmol) in naive animals pretreated with the angiotensin converting enzyme inhibitor, captopril caused a small increase in paw volume (0.04 +/- 0.003 ml, mean +/- s.e. mean, n = 6), while the B2-selective agonist, tyrosine8-bradykinin (T-BK, 3 nmol) induced marked oedema (0.36 +/- 0.02 ml). However, i.pl. injection of DABK (3-300 nmol) in rats pretreated with LPS (24 h beforehand) resulted in a marked dose- and time-related increase in paw volume, with mean ED50 of 24.1 nmol. In contrast, oedema caused by T-BK (3 nmol) was reduced by 79 +/- 4% in animals treated with LPS when compared with naive animals. 3. Oedema caused by prostaglandin E2 (PGE2, 10 nmol) was unaffected by LPS treatment, while oedema induced by histamine (100 nmol), 5-hydroxytryptamine (5-HT, 10 nmol) and substance P (SP, 3 nmol) was reduced (P < 0.05). 4. The selective B1 antagonist, des-Arg9[Leu8]-BK (100-300 nmol), produced dose-dependent inhibition of DABK (100 nmol)-induced paw oedema in LPS-treated animals with mean IC50 of 134 nmol, while the selective B2 antagonists, Hoe 140 and NPC 17731 (each 10 nmol), had no effect. 5. Treatment of animals with dexamethasone (0.5 mg kg-1, s.c.) 24 or 48 h prior to LPS injection resulted in a graded inhibition of DABK (100 nmol)-induced oedema formation (58 +/- 3 and 82 +/- 2%, respectively), and almost reversed to control value oedema formation induced by T-BK (3 nmol) in LPS-pretreated rats. Cycloheximide (1 mg kg-1, s.c.) or indomethacin (2 mg kg-1, i.p.) pretreatment 24 and 1 h prior to LPS injection, respectively, markedly inhibited DABK (100 nmol)-induced paw oedema (98 +/- 2 and 50 +/- 4%, respectively). 6. Intraplantar injection of submaximal dose of DABK (10 nmol) in LPS-treated rats produced modest paw oedema (0.09 +/- 0.03 ml). However, i.pl. injections of PGE2, prostacyclin (PGI2), calcitonin-gene-related peptide (CGRP), SP, 5-HT, or platelet activating factor (PAF) (each 1 nmol), which alone caused little or no paw oedema, resulted in a potentiation of the DABK-induced oedema. The increases in paw volume (in ml) were: PGE2 + DABK (0.31 +/- 0.03), PGI2 + DABK (0.39 +/- 0.02), CGRP+DABK (0.35 +/- 0.04), DABK+SP (0.33 +/- 0.04), DABK + 5-HT (0.40 +/- 0.02) and DABK+PAF (0.38 +/- 0.016) ml. In contrast, histamine (1 nmol) was ineffective in potentiating the response to DABK. 7. The selective B1 receptor antagonist, DALBK (100-300 nmol), produced dose-dependent inhibition of paw oedema potentiation induced by co-injection of DABK and other mediators with mean ID50S (nmol) of: 180, 160, 139 and 135 in the presence of PGE2, PGI2, SP and 5-HT, respectively. 8. These results demonstrate that DABK-induced increase in paw volume in LPS-treated rats is probably mediated by induction of B1 receptors, associated with downregulation of B2 receptors. The induction of B1 receptors by LPS is sensitive to dexamethasone and cycloheximide treatment and requires activation of cyclo-oxygenase pathway. In addition, B1 receptors, when upregulated following LPS treatment, can interact in a synergistic manner with several inflammatory mediators such as PGI2, PGE2, CGRP, PAF and 5-HT. Such results indicate that induction of the B1 receptor might have a significant pathophysiological role in modulating chronic inflammatory diseases.
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PMID:Upregulation of B1 receptor mediating des-Arg9-BK-induced rat paw oedema by systemic treatment with bacterial endotoxin. 885 92

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

1. Changes in the release of nitric oxide (NO) in vivo were studied in rats following the administration of endothelium-dependent and -independent vasodilators as well as the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). NO production was assessed by measuring variations of nitrate in plasma by capillary ion analysis. 2. Intravenous administration of the endothelium-dependent vasodilators, bradykinin (2 and 10 micrograms kg-1 min-1) or substance P (0.3-3 micrograms kg-1 min-1) caused a transient dose-dependent hypotension followed by an increase in plasma nitrate concentration (maximal increments: 33 +/- 5% and 38 +/- 6%, for bradykinin and substance P, respectively). Prior administration of L-NAME (10 mg kg-1 min-1) inhibited the hypotension and increase in plasma nitrate caused by these substances. Intravenous administration of sodium nitrate (200 micrograms kg-1) also produced a transitory elevation in plasma nitrate which was similar in magnitude as that caused by the vasodilators. A rapid and transitory increment in plasma nitrate was observed after i.v. administration of authentic NO (400 micrograms kg-1). 3. Rats receiving the endothelium-dependent vasodilators, prostacyclin (0.6 micrograms kg-1 min-1) or adenosine (3 mg kg-1 min-1) intravenously showed a drop in blood pressure paralleled by a decrease in plasma nitrate (maximal decreases: 34 +/- 5% and 24 +/- 4%, for prostacyclin and adenosine, respectively). A similar effect on the plasmatic concentration of nitrate was observed when L-NAME (10 mg kg-1 min-1, i.v.) was administered to the animals. 4. This study demonstrates that (i) changes in plasma nitrate can be detected in vivo after stimulation or inhibition of NO synthase, (ii) an increased production of NO, measured as plasma nitrate, is related to the hypotension caused by bradykinin and substance P and (iii) a diminished concentration of plasmatic nitrate is associated to the hypotension induced by adenosine or prostacyclin (endothelium-independent vasodilators), suggesting that the L-arginine: NO pathway is capable of rapid down-regulation in response to a fall in blood pressure.
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PMID:Changes in nitric oxide release in vivo in response to vasoactive substances. 893 25

Ion channels play key roles in determining smooth muscle tone by setting the membrane potential and allowing Ca2+ influx. Perhaps not surprisingly, therefore, they also provide targets for neurotransmitters and other messengers that act on smooth muscle. Application of patch-clamp and molecular biology techniques and the use of selective pharmacology has started to provide a wealth of information on the ion channel systems of smooth muscle cells, revealing complexity and functional significance. Reviewed are the actions of messengers (e.g., noradrenaline, acetylcholine, endothelin, angiotensin II, neuropeptide Y, 5-hydroxytryptamine, histamine, adenosine, calcitonin gene-related peptide, substance P, prostacyclin, nitric oxide and oxygen) on specific types of ion channel in smooth muscle, the L-type calcium channel, and the large conductance Ca(2+)-activated, ATP-sensitive, delayed rectifier and apamin-sensitive K+ channels.
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PMID:Actions of neurotransmitters and other messengers on Ca2+ channels and K+ channels in smooth muscle cells. 913 20

We have previously reported that neuropeptide Y (NPY) inhibits responses induced by various agonists (noradrenaline, vasoactive intestinal peptide, substance P,5-hydroxytryptamine) in isolated guinea pig trachea. Although the underlying mechanisms have not been fully characterized, it was found that the NPY-evoked inhibition was specifically expressed with agents for which locally released prostaglandins (PGs) are important determinants for their myotropic activity. In the present study, we have extended these findings by examining whether NPY was capable of regulating the release of prostacyclin and thromboxane A2 induced by bradykinin (BK) from naive and ovalbumin-sensitized guinea pig perfused lungs. Our results showed that infusion of NPY (0.24 microM) through the lung significantly inhibited the release of 6-keto-PGF1 alpha (> 30%) and thromboxane B2 (50%) induced by intraarterial administration of BK (3 micrograms) from untreated and ovalbumin-sensitized guinea pig perfused lung. However, the inhibitory effect of NPY was lost in the immunological production of prostaglandins. These results suggest that NPY may act as a regulatory agent of the release of cyclooxygenase-derived products by possibly acting on events preceding phospholipase A2 activation.
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PMID:Effect of neuropeptide Y on bradykinin-induced release of prostacyclin and thromboxane from guinea pig perfused lung. 927 48

Estrogen is known to improve in the short term the impaired endothelium-dependent vasodilating responses in postmenopausal women, which may account in part for the beneficial cardiovascular effects of the female hormone. Endothelium-dependent vasodilation is achieved by combined effects of endothelium-derived prostacyclin, nitric oxide (NO), and hyperpolarizing factor. In this study, we investigated our hypothesis that short-term estrogen improves both NO-mediated and non-NO-mediated endothelium-dependent vasodilation in postmenopausal women. The study included 12 postmenopausal women (aged 64 +/- 3 years). The forearm blood flow was measured by strain-gauge plethysmography. The forearm vascular responses to the endothelium-dependent vasodilators, acetylcholine and substance P, were examined before and after intravenous administration of conjugated estrogen and subsequently after intraarterial infusion of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis. Short-term estrogen augmented the forearm vasodilating responses to both acetylcholine and substance P. The treatment with L-NMMA almost abolished the augmented response to acetylcholine but did not affect that to substance P. The forearm vascular response to sodium nitroprusside was unchanged by the estrogen administration. These results indicate that estrogen augments (in the short-term) both NO-mediated and non-NO-mediated endothelium-dependent forearm vasodilation in postmenopausal women. Thus the beneficial effect of estrogen on endothelial vasodilator function appears to extend to non-NO-dependent mechanism(s).
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PMID:Short-term estrogen augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilation in postmenopausal women. 933 8


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