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)

Idrapril is the prototype of a new chemical class of angiotensin converting enzyme (ACE) inhibitors, the hydroxamic non-amino acid derivatives. Idrapril strongly inhibited rat and human plasma ACE and rabbit lung ACE (IC50: 7-12 nM) as well as the pressor response induced by angiotensin I in anesthetized rats (ED50: 63 nmol/kg i.v.). Idrapril (0.04-23 mumol/kg i.v.) lowered the blood pressure dose dependently, up to 20-35%, in different models of hypertension (sodium-depleted spontaneously hypertensive rat, two-kidney-one-clip renal hypertensive rat, and aortic-coarctated rat), its profile being similar to that of captopril in terms of potency and efficacy. Idrapril and captopril reduced the blood pressure and potentiated substance P-induced bronchoconstriction in the guinea pig to the same extent, suggesting a similar degree of ACE inhibition in the circulation. However, idrapril potentiated capsaicin-induced bronchoconstriction (a model that has been related to the liability of ACE inhibitors to produce cough in patients) less effectively than captopril. We conclude that effective ACE inhibition in vitro and in vivo can be obtained with this novel class of compounds.
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PMID:Pharmacology of idrapril: a new class of angiotensin converting enzyme inhibitors. 138 23

1. The effect of an acetly-coA lysolecithin acyltransferase inhibitor, thimerosal, on the release of endothelium-derived relaxing factor (EDRF) was examined in the greyhound isolated coronary artery. 2. Thimerosal (1-10 microM) relaxed fully, ring segments of coronary artery which were contracted with the thromboxane A2-mimetic, U46619 (30 nM). The response was endothelium-dependent, slow in both onset and time to reach maximum. The maximum relaxation to the highest concentration of thimerosal (10 microM) was maintained for 10-20 min before the tissue slowly regained active force (1-2 h) to the same or higher level as that prior to the addition of thimerosal. At this time the endothelium-dependent relaxation responses to acetylcholine (ACh), substance P (SP), bradykinin (BK) and the calcium ionophores, ionomycin and A23187 were abolished. The endothelium-dependent contractions to the nitric oxide synthase inhibitors, NG-nitro-L-arginine (L-NNA; 10-100 microM) and NG-monomethyl-L-arginine (L-NMMA: 10-100 microM), however, were unaffected. 3. Thimerosal (10 microM) did not affect the relaxation curve to sodium nitroprusside (SNP) nor the contraction curve to the thromboxane A2-mimetic, U46619. 4. Both the relaxation response to thimerosal and the selective block of the relaxation responses to stimulated EDRF release were unaffected by either indomethacin (10 microM) or superoxide dismutase (150 u ml-1). 5. L-NNA (100 microM) significantly blocked the relaxation curves to thimerosal and A23187 but not that to SNP.6. Abolition of stimulated EDRF-mediated responses with thimerosal was unlikely to result from maximal and maintained stimulation of EDRF release even when active U46619-induced force had returned to pre-thimerosal levels, since the relaxation curves to glyceryl trinitrate (GTN) and SNP were markedly attenuated in the presence of SNP and GTN respectively when active force was restored with endothelin-1 (ET-1).7. Melittin (1 microM), ionomycin (1 microM) and A23187 (1 microM) each had selective effects on stimulated but not basal EDRF responses, similar to those of thimerosal.8. We propose that stimulated but not 'basal' release of EDRF is dependent on the release of arachidonic acid or one of its non-cyclo-oxygenase metabolites, possibly by Ca2'-dependent activation of phospholipase A2.
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PMID:Thimerosal blocks stimulated but not basal release of endothelium-derived relaxing factor (EDRF) in dog isolated coronary artery. 138 15

1. The effects of L-NG-nitroarginine (L-NOARG) and L-NG-nitroarginine methyl ester (L-NAME) on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig coronary bed, by use of a Langendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The vasodilator responses evoked by low doses of 5-HT (5 x 10(-10)-10(-8) mol) were almost abolished by L-NAME and L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M), although L-NOARG (3 x 10(-5) M) was significantly less potent than L-NAME (3 x 10(-5) M) as an inhibitor of vasodilator responses to 5-HT (5 x 10(-8) mol). 3. The vasodilator responses evoked by substance P (5 x 10(-12)-5 x 10(-9) mol) were reduced in the presence of L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) M). The response to substance P was almost abolished by L-NAME and L-NOARG (both at 10(-4) M). 4. The amplitude of the vasodilator responses to ATP (5 x 10(-11) and 5 x 10(-9)-5 x 10(-7) mol) was little affected by either L-NAME or L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M).7. It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibiting the vasodilator actions of 5-HT and ATP in this preparation.
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PMID:Effects of nitric oxide synthase inhibitors, L-NG-nitroarginine and L-NG-nitroarginine methyl ester, on responses to vasodilators of the guinea-pig coronary vasculature. 138 16

1. Substance P (SP) and dopaminergic nerves have been described in the kidney. In the brain, SP increases dopamine production. In the kidney, SP increases sodium excretion. 2. Intrarenal dopamine acts as an endogenous natriuretic hormone. It is possible that dopamine could mediate the natriuretic effect of SP. 3. We therefore studied the effect of the intrarenal arterial infusion of SP (0.1, 1.0, 10 ng kg body wt-1 min-1) on mean arterial pressure (MAP), renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), absolute (UNaV) and fractional (FENa) sodium excretion as well as dopamine and noradrenaline excretion in dogs. Since dopamine is not natriuretic in hydropaenic states, studies were performed during hydropaenic and saline loaded states. 4. During hydropaenia, SP increased RBF, GFR, and V in a dose-related fashion but did not alter UNaV or FENa. Urinary noradrenaline was not affected but urinary dopamine decreased with increasing doses of SP. MAP was not affected. 5. During saline loading, SP increased RBF, GFR, V, UNaV, and FENa in a dose-related fashion. Both urinary noradrenaline and urinary dopamine increased. The fractional excretion of sodium correlated with dopamine but not noradrenaline excretion. MAP was not affected. 6. The renal haemodynamic and functional effects of SP may be mediated by SP-associated increases in urinary dopamine.
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PMID:Contrasting effect of substance P on renal function and dopamine excretion in hydropaenic and volume expanded dogs. 138 39

Ultraviolet-visible spectroscopy has been used as a rapid method to evaluate the hydrophobic interactions between a series of cationic and zwitterionic neuropeptides and dipeptides with the hydrophobic core of two membrane model systems; sodium dodecyl sulfate and lysophosphatidylcholine micelles. If a hydrophobic interaction occurs, a 1-nm bathochromic shift is observed in the uv-visible spectrum of the aromatic side chains when going from aqueous solution to a micellar solution. The aromatic residues of substance P, bradykinin, and Des-Arg9 bradykinin all exhibited the 1-nm bathochromic shift in the presence of sodium dodecyl sulfate while those of Met-enkephalin did not. The opposite effects were observed in the presence of lysophosphatidylcholine micelles.
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PMID:The use of UV-visible spectroscopy for the determination of hydrophobic interactions between neuropeptides and membrane model systems. 142 Sep 72

One of the initial events in pulpal inflammation has been characterized as neurogenic inflammation: the release of neuropeptides following excitation of sensory C-fibers by noxious stimuli which alters microcirculatory parameters, that is, vasodilation and plasma extravasation. Thus, the purpose of the study was to investigate the effect of capsaicin on pulpal blood flow (PBF) with the aim of understanding neurogenic inflammation in the dental pulp by characterizing the response of the pulpal vasculature to repeated applications of various concentrations of capsaicin. Experiments were performed on canine teeth of cats anesthetized with sodium pentobarbital. PBF was measured by the laser Doppler flowmeter following the application of capsaicin into the dentinal cavities of the canine teeth. The increases of PBF to capsaicin were 31.8 +/- 6.3% (n = 6) and 54.2 +/- 6.2% (n = 9), for 1 microM and 100 microM capsaicin, respectively. The increase of PBF peaked at about 50 sec after the capsaicin placement and the PBF returned to control level within 20 min following capsaicin removal. Four repeated applications of 1 microM capsaicin caused a small change in the peak PBF amplitude. In contrast, a second application of 100 microM capsaicin caused a significantly smaller increase of PBF than the first application (26.8 +/- 6.4% vs. 54.2 +/- 6.2%). Results of the present study show that local application of capsaicin caused the increase of PBF and that repeated capsaicin stimulations inhibited PBF responses. Smaller PBF increases in response to high concentrations of capsaicin also suggested the depletion of vasoactive substances, e.g. substance P, from the sensory nerve terminals, which appears to be dose-dependent. The PBF response to capsaicin suggests that neurogenic inflammation in the dental pulp involves capsaicin-sensitive nerve endings.
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PMID:The effects of capsaicin on pulpal blood flow. 150 4

The ability of Acetylcholine (ACh) and A23187 to induce endothelium-dependent relaxation was compared in the isolated perfused mesenteric arterial bed of untreated adult rats, adult rats treated neonatally with capsaicin, and adult rats treated as adults with capsaicin. Following neonatal capsaicin treatment, the response to both agents was reduced. Following adult treatment, the response to both agents was reduced seven days following capsaicin treatment. The same results were obtained in the presence of L-arginine or indomethacin. Tissues from all rats responded equally to sodium nitroprusside. Following capsaicin treatment no change in the structural relationship of the arterial intima was detected but no perivascular nerve fibres immunoreactive to substance P (SP) or calcitonin gene-related peptide (CGRP) could be demonstrated. It is suggested that the reduced response to ACh and A23187 does not involve a change in endothelial muscarinic receptors or a structural change in the arterial intima, but is directly related to the absence of immunohistochemically demonstrable CGRP/SP-containing perivascular innervation.
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PMID:Peptidergic nerve involvement in the control of endothelium-dependent vascular relaxation. 152 74

Central injection of the tachykinins (TKs) neurokinin A (NKA), eledoisin (ELE), and kassinin (KASS) produced long-lasting inhibition (up to 6 h) of drinking induced by subcutaneous hypertonic NaCl, while substance P (SP) and physalaemin (PHYS) evoked short-lasting effects. The hypothesis that water retention or increased Na+ excretion by the kidney (induced by TKs) may reduce the need for water ingestion was tested. The results obtained both in urine collection experiments and in nephrectomized rats showed that the duration of the effect of NKA, ELE, and KASS is not due to water retention or increased Na+ excretion by the kidney. The effect of NKA, but not that of ELE and KASS, was shortened by nephrectomy, even though NKA did not modify urine volume or Na+ excretion. Indomethacin pretreatment, like nephrectomy, reduced the duration of the NKA effect, suggesting that renal prostaglandins are involved in it. On the other hand, the long-lasting effect of the three TKs cannot be easily explained in terms of slow metabolic degradation, particularly for NKA. Alternatively, it might be hypothesized that these TKs produce a modification of osmoreceptor function lasting well beyond the life of the peptide, and/or that they produce Na+ loss through emunctories different from the kidney.
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PMID:Inhibition of cell dehydration-induced drinking by tachykinins: evaluation of possible renal effects accounting for the long-lasting inhibition. 152 99

Steroids (aldosterone and testosterone) and peptides of cerebral origin (angiotensin II and the tachykinins) control the salt intake of the rat. They arouse or suppress the behaviour and produce life-long enhancements of NaCl intake. Need-induced salt intake (salt appetite or salt hunger), which is the consequence of sodium deficiency, is aroused by a synergy within the brain of cerebral angiotensin II and aldosterone. And prior episodes of sodium depletion produce enhancements of subsequent salt appetites, but only if the prior depletions were accompanied by angiotensin II and aldosterone action. Need-free salt intake, which occurs daily when the rat is in positive sodium balance, is inherently high in the rat and is organized in the perinatal period by aromatized testosterone which suppresses the intake of the male. It is also enhanced by prior activations of angiotensin II and aldosterone. Both need-induced and need-free salt intake are suppressed by intracranial tachykinins. Non-mammalian tachykinins (eledoisin, physalaemin, kassinin) are both antidipsogenic and antinatriorexigenic, but amino-senktide, an analogue of the mammalian tachykinin substance P with selective affinity for the NK 3 receptor, appears to be a selective antinatriorexigenic agent, and could provide a rational therapy for chronic overconsumption of salt.
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PMID:Control of salt intake by steroids and cerebral peptides. 163 90

The molecular forms of angiotensin converting enzyme (ACE; EC 3.4.15.1) in preparations of pig brain cortical microvessels and striatal synaptosomal membranes have been identified by immunoelectrophoretic blot analysis. The cortical microvessels contained only the endothelial form of the enzyme, Mr 180,000, which comigrated with pig kidney ACE on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In contrast, the synaptosomal membranes contained only a smaller form of ACE, Mr 170,000, which represents the neuronal form of the enzyme. No significant differences in inhibitor sensitivity or substrate specificity were detected between the two forms of ACE. In particular, neurokinin A was resistant to hydrolysis by either microvessel or synaptosomal membrane ACE, and the pattern of hydrolysis of substance P by the two preparations was identical.
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PMID:Characterization of neuronal and endothelial forms of angiotensin converting enzyme in pig brain. 164 60


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