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 ability of the angiotensin antagonists 1-Sar,8-Ala-angiotensin II (saralasin) and 1-Sar,8-Leu-angiotensin II (sarleusin) and the bradykinin-potentiating peptide B (BPP) to modify the twitch-enhancing effect of angiotensin II, bradykinin, and substance P, was studied in the isolated field-stimulated guinea-pig vas deferens. The twitch-enhancing effect of angiotensin, bradykinin and substance P underwent tachyphylaxis which was strongest after angiotensin. Saralasin and sarleusin were without influence on the twitch response and antagonized the effect of angiotensin, but not that of bradykinin or substance P, respectively. The features of the antagonism to angiotensin were compatible with the notion that saralasin is a competitive and sarleusin a dual antagonist. BPP did modify either the twitch response or the effects of angiotensin, bradykinin, and substance P. In the non-stimulate vas, the contracting effect of noradrenaline did not undergo tachyphylaxis and was not mofified by angiotensin, bradykinin, or substance P. It is concluded that there exist in the guinea-pig vas specific peptide receptors, one of them having the properties of a "typical" angiotensin receptor.
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PMID:An attempt to differentiate the effects of angiotensin II, substance P and bradykinin on the field-stimulated guinea-pig vas deferens. 46 11

The central cardiovascular and dipsogenic effects of angiotensin II involve interactions with norepinephrine, dopamine, and serotonin. Our findings that angiotensin II receptors and substance P immunoreactivity show a parallel distribution in the dorsal medulla and that angiotensin II releases substance P from perfused rat medulla slices revealed the potential for a functional relation between these peptidergic systems as well. Additional evidence suggests that the heptapeptide angiotensin-(1-7) exerts its biological activities via selective angiotensin receptor subtypes. Thus, we compared the effects of these two peptides on release of substance P and monoamines in perfused slices of medulla and hypothalamus from 77 male Sprague-Dawley rats. Transmitter levels were determined in 6-minute collections of perfusate before (basal), during (experimental), and after (recovery) perfusion with either angiotensin-(1-7), angiotensin II, or Krebs' solution alone (control). Substance P was measured by radioimmunoassay and monoamines and their metabolites by high-performance liquid chromatography with electrochemical detection. In the medulla, 2 microM angiotensin II but not angiotensin-(1-7) significantly increased efflux of substance P (221 +/- 87% of basal) and norepinephrine (130 +/- 17% of basal) during the experimental period. The effect of angiotensin II on substance P was sustained into the recovery period. Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were not detected in this brain region. In the hypothalamus, both angiotensin-(1-7) and angiotensin II increased substance P (169 +/- 30% and 141 +/- 35% of basal, respectively); the effect of angiotensin II was sustained throughout the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential actions of angiotensin II and angiotensin-(1-7) on transmitter release. 134 28

2-n-Butyl-4-chloro-5-hydroxy-methyl-1-[(2'-(1H)-tetrazol-5-yl)biph enyl-4- yl)methyl]imidazol potassium salt (DuP 753) is a nonpeptide angiotensin II receptor antagonist that inhibits the contractile effects of angiotensin II competitively and shows pA2 values of 8.27 on the rabbit aorta and jugular vein, 8.66 on the rat portal vein and stomach, 8.19 on the rat urinary bladder, and 8.36 on human colon, ileum, and urinary bladder. This agent (more than 10(-5) M) exhibits no agonistic activity and does not affect the contractile effects of norepinephrine, acetylcholine, bradykinin, desArg9-bradykinin, substance P, neurokinin A, neurokinin B, or bombesin in the various tissues. The present results demonstrate that DuP 753 is a potent nonpeptide antagonist with high affinity, specificity, and selectivity for the angiotensin receptor.
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PMID:DuP 753 is a specific antagonist for the angiotensin receptor. 167 62

The proposal that the mas oncogene is an angiotensin receptor was evaluated in Xenopus oocytes injected with human and rat mas RNA transcripts, and during transient expression of mas in several cell lines. No evidence of mas-induced angiotensin II (AII) receptors or [Ca2+]i responses was observed in Xenopus oocytes or in most of the transfected cells. However, Cos-1 cells, which showed a small endogenous [Ca2+]i response to AII, exhibited a modest but reproducible enhancement of this response after mas transfection. Such responses were inhibited by [Sar1, Ala8]AII and [Sar1, Ile8]AII, but not by [D-Arg1, D-Pro2, D-Trp7,9, Leu11] substance P, an antagonist reported to inhibit mas-induced responses to AII in oocytes. These findings are not compatible with the proposal that the mas oncogene is an angiotensin receptor, but suggest that expression of mas leads to increased responsiveness of the endogenous AII signaling system.
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PMID:The mas oncogene enhances angiotensin-induced [Ca2+]i responses in cells with pre-existing angiotensin II receptors. 172 43

There is increasing evidence that neuropeptides have trophic functions during embryogenesis. We examined the ability of angiotensin II, substance P, somatostatin-28 and luteinising hormone-releasing hormone to influence neurite outgrowth from embryonic chick sympathetic neurons in culture. Nanomolar concentrations of angiotensin II inhibited neurite outgrowth, whereas the other peptides had no effect at similar concentrations. The effect of angiotensin II on neurite outgrowth is likely to be mediated by an atypical angiotensin receptor, as it was only weakly inhibited by [sar1,ala8]angiotensin II, and was not inhibited by losartan, an inhibitor of mammalian AT1 receptors, or PD123319, an AT2 inhibitor. Neurite outgrowth was also inhibited by angiotensin III and angiotensin IV but not by angiotensinogen I1-14. The study provides further evidence that angiotensin peptides, like classical neurotransmitters, may have trophic functions during embryogenesis.
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PMID:A novel action of angiotensin peptides in inhibiting neurite outgrowth from isolated chick sympathetic neurons in culture. 880 32

Activation of the renin-angiotensin-aldosterone system (RAAS) in left ventricular systolic dysfunction is a critically important determinant in the pathophysiologic processes that lead to progression of heart failure and sudden death. Angiotensin II, acting at the specific angiotensin receptor (AT1-R), activates a series of intracellular signaling sequences which are ultimately expressed within the cardiovascular system as vasoconstriction and associated vascular hypertrophy and remodeling. Angiotensin converting enzyme (ACE) inhibition leads to increases in the vasodilatory peptides bradykinin and substance P and at least an initial reduction in angiotensin II concentrations. AT1-R blocking drugs prevent access of angiotensin II to the AT1-R and thus prevent cellular activation. ACE inhibitors have clearly been demonstrated through a large number of clinical trials to increase survival in congestive heart failure, primarily by reducing the rate of progression of left ventricular dilatation and decompensation. However, this beneficial effect diminishes over time. Preliminary short-term clinical studies evaluating the efficacy of AT1-R blocking drugs in the treatment of heart failure have suggested that they elicit similar hemodynamic and neuroendocrine effects as do the ACE inhibitors. The combination ACE inhibitors and AT1-R blocking drugs offer the theoretical advantage of increasing bradykinin while blocking the actions of angiotensin II, and thus possibly show a synergistic effect. Again, preliminary studies have yielded encouraging results that are difficult to interpret because neither ACE inhibitor nor the AT1-R blocking drug doses were titrated to tolerance. Pharmacological manipulation of the RAAS has led to better understanding of its role in heart failure and improved clinical outcomes.
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PMID:Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of heart failure caused by left ventricular systolic dysfunction. 1036 49

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers antagonists (ARAs) are widely used compounds in various cardiovascular disorders. ACEIs, but not ARAs, inhibit the enzyme dipeptidyl carboxypeptidase which is involved in the conversion of angiotensin I to II and degradation of kinins like bradykinin and substance P. Bradykinin and substance P are potent mediators of inflammation and pain. Hence the study was undertaken to evaluate the effects of captopril (an ACEI) and losartan (an ARA-AT1 receptor antagonist) on thermal and chemical induced nocioception by employing hot plate and acetic acid induced writhing tests respectively in mice. Inbred albino mice weighing between 25-30 g were used and they were divided into two sets, each set containing 7 groups. Control groups received normal saline and the remaining six groups received three doses (0.5, 1 and 2 mg/kg) of captopril and three doses (0.5, 1 and 2 mg/kg) of losartan. Drugs were administered intraperitoneally fifteen minutes before placing the animal over the hot plate or 30 minutes before injecting 0.6% acetic acid. Both drugs dose dependently reduced the reaction time in hot plate method. In chemical induced writhing test, both the drugs reduced the latency of onset of writhing and in captopril pretreated groups, acetic acid induced sustained abdominal contraction without any intermittent relaxation. However, in losartan pretreated animals acetic acid just increased the number of writhings without sustained abdominal contraction. Thus, our study suggests that both drugs have hyperalgesic effects.
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PMID:Effects of captopril and losartan on thermal and chemical induced pain in mice. 1705 37

Summary The central nervous system (cerebral ganglion) of adult ascidians is linked to the neural gland complex (NGC), which consists of a dorsal tubercle, a ciliated duct and a neural gland. The function of the NGC has been the subject of much debate. The recent publication of the complete genomic sequence of Ciona intestinalis provides new opportunities to examine the presence and distribution of protein families in this basal chordate. We focus here on the ascidian neuropeptide G-protein-coupled receptors (GPCRs), the vertebrate homologues of which are involved in homeostasis. In situ hybridization revealed that five Ciona GPCRs [vasopressin receptor, somatostatin receptor, CRH (corticotropin-releasing hormone) receptor, angiotensin receptor and tachykinin receptor] are expressed in the NGC of adult ascidians. These findings, together with histological and ultrastructural data, provide evidence to support a role for the ascidian NGC in maintaining ionic homeostasis. We further speculate about the potential similarities between the ascidian NGC and the vertebrate choroid plexus, a neural peri-ventricular organ.
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PMID:Morphological and gene expression similarities suggest that the ascidian neural gland may be osmoregulatory and homologous to vertebrate peri-ventricular organs. 1707 50

In the present study the existence of a non-AT(1), non-AT(2) angiotensin (Ang) binding site unmasked by the organomercurial protease inhibitor p-chloromercuribenzoate (PCMB) was demonstrated in mouse brain membranes, consistent with observations previously reported in the rat (Karamyan and Speth, 2007b). The pharmacological specificity of the non-AT(1), non-AT(2) angiotensin binding site was similar to the rat brain: Sar(1)-Ile(8)-Ang II > Ang III >or= Ang II > Ang I> p-aminophenylalanine(6) Ang II> CGP42112 >> Ang IV > Ang 1-7 congruent with shorter angiotensin fragments. Neurotensin, bradykinin, and luteinizing hormone-releasing hormone showed K(i) values >10 microM, while substance P and VIP had K(i) values of approximately 2 microM. The non-AT(1), non-AT(2) angiotensin binding site was not present in adrenal, liver or kidney. Subcellular fractionation showed a higher density of [(125)I]Ang II binding in plasma membrane (P2) fractions of cerebral cortex and hypothalamus relative to debris (P1) fractions. The binding site is present in the brains of mice in which the AT(1a), AT(1b), AT(2), Mas, and neprilysin (EC 3.4.24.11, neutral endopeptidase) was knocked out confirming that the binding site is not a heretofore described angiotensin receptor or neprilysin. These observations confirm that this novel Ang binding site is distinct from classical AT(1), AT(2), AT(4) and Ang 1-7 receptors while retaining a high specificity for angiotensins that act on the known angiotensin receptors. Whether this binding site functions as a novel receptor for angiotensins or a specific angiotensinase with variable functionality at different redox states will require further study.
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PMID:Characterization of the brain-specific non-AT(1), non-AT(2) angiotensin binding site in the mouse. 1857 43

Dipeptidyl peptidase-IV (DPP-IV) inhibitors decrease degradation of the incretins. DPP-IV inhibitors also decrease degradation of peptides, such as substance P, that may be involved in the pathogenesis of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. This study tested the hypothesis that DPP-IV inhibition affects risk of clinical angioedema, by comparing the incidence of angioedema in patients treated with the DPP-IV inhibitor vildagliptin versus those treated with comparator in Phase III randomized clinical trials. Prospectively defined angioedema-related events were adjudicated in a blinded fashion by an internal medicine adjudication committee and expert reviewer. Concurrent ACE inhibitor or angiotensin receptor blocker exposure was ascertained from case report forms. Study drug exposure was ascertained from unblinded data from phase III studies. Odds ratios and 95% confidence intervals comparing angioedema risk in vildagliptin-treated and comparator-treated patients were calculated for the overall population and for patients taking ACE inhibitors or angiotensin receptor blockers, using both an analysis of pooled data and a meta-analysis (Peto method). Overall, there was no association between vildagliptin use and angioedema. Among individuals taking an ACE inhibitor, however, vildagliptin use was associated with an increased risk of angioedema (14 confirmed cases among 2754 vildagliptin users versus 1 case among 1819 comparator users: odds ratio 4.57 [95% confidence interval 1.57 to 13.28]) in the meta-analysis. Vildagliptin use may be associated with increased risk of angioedema among patients taking ACE inhibitors, although absolute risk is small. Physicians confronted with angioedema in a patient taking an ACE inhibitor and DPP-IV inhibitor should consider this possible drug-drug interaction.
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PMID:Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. 1958 3


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