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 anti-inflammatory and analgesic profile of a new topical foam formulation of ketoprofen lysine salt (CAS 57469-78-0, Artrosilene Schiuma, KLS-foam) was characterized in comparison with marketed gel formulations containing KLS (KLS-gel) or diclofenac diethylammonium salt (DCF-gel). KLS-foam dose-dependently inhibited oedema formation and hyperalgesia induced by subplantar injection of carrageenan or substance P, being more potent than KLS-gel. At equieffective anti-inflammatory doses, KLS-foam provided a more pronounced analgesic effect than DCF-gel. KLS-foam also markedly inhibited exudate formation and prostaglandin production induced by subcutaneous implantation of carrageenan soaked sponges. In carrageenan induced paw inflammation, KLS-foam provided the same anti-inflammatory effect as orally administered KLS, but induced significantly less gastric damages. Oral administration of KLS resulted in sustained systemic absorption of ketoprofen, whereas after topical application of KLS-foam no appreciable ketoprofen plasma levels were detected. These data support the anti-inflammatory and particularly the analgesic effectiveness of the new foam formulation of KLS, a finding that, together with the high gastric tolerability, further emphasizes the usefulness of KLS-foam in the treatment of localized flogistic diseases and associated pain.
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PMID:Effects of a new foam formulation of ketoprofen lysine salt in experimental models of inflammation and hyperalgesia. 754 96

The successful introduction of angiotensin converting enzyme (ACE) inhibitors in the treatment of patients with essential hypertension or heart failure has increased interest in the (patho)physiological role of the renin-angiotensin system (RAS). ACE is not only involved in the formation of angiotensin II from angiotensin I, but also inactivates vasoactive substances such as bradykinin and substance P. Accumulation of these substances during treatment with ACE inhibitors may contribute to both their therapeutic action and certain adverse effects associated with their use, such as cough and angioneurotic oedema. Renin inhibitors offer an alternative approach to inhibit the RAS. The major advantage of these, still experimental, drugs is their high specificity for the RAS since angiotensinogen is the only known substrate of renin. The currently available renin inhibitors are pseudopeptides that are rapidly taken up by the liver and excreted in the bile. Consequently, these drugs are subjected to a considerable first pass effect which limits their oral bioavailability. Additionally, plasma elimination half-life times are short and the duration of action is limited. Despite these shortcomings, single oral or intravenous administration results in a 80 to 90% inhibition of plasma renin activity and a slight reduction in blood pressure in patients with hypertension. The extent of blood pressure reduction is dependent on the patient's salt balance. After 1 week of oral treatment with the renin inhibitor remikiren, the antihypertensive effect was reduced in salt-repleted hypertensive patients. Subsequent intravenous administration of the drug did not further affect blood pressure, indicating that it was not the first pass effect that was limiting the efficacy of remikiren.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacokinetics and efficacy of renin inhibitors. 758 99

Substance P, which is present in small nerve terminals and proximal to microvessels in rat strated muscle, may have a vasodilator role if released into the microcirculation. Male, Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and the cremaster muscle, with intact blood supply and innervation, was suspended in a bath containing a physiological salt solution. The major autonomic innervation to the cremaster (genito-femoral nerve) was isolated and its cut, distal end was stimulated (3-5 Hz, 2 ms, 10-20 V). Diameters of third order arterioles (14-23 microns) were measured by television microscopy. Stimulation after a 20-min pretreatment with the alpha-adrenergic receptor antagonist phentolamine (2.10(-5) M) unmasked a moderate vasodilation, which was attenuated by treatment with the substance P receptor antagonist [D-Arg1,D-Pro2, D-Trp7,9,Leu11]-substance P (1.10(-6) M). This neurogenic vasodilation was not sensitive to muscarinic receptor blockade by atropine (1.10(-4) M), but was partially blocked by the beta-adrenergic receptor antagonist propranolol (1.10(-5) M). These data suggest that the rat striated muscle microvasculature is innervated with nerves containing substance P, and the release of substance P from the nerve terminals causes arteriolar dilation.
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PMID:Neural release of substance P causes dilation of arterioles in rat striated muscle. 767 38

CP 96,345 is a nonpeptide high affinity antagonist of the substance P (NK1) receptor. The radiosynthesis of [11C]CP 96,345 suitable for Positron Emission Tomography (PET) applications is described. [11C]CP 96,345 was prepared by O-methylation of a desmethyl precursor via in situ generation of its phenolate salt. The in vivo tissue distribution of [11C]CP 96,345 in guinea pigs (n = 2) at 5 and 30 min was determined. Uptake was low in brain (approximately 0.04% dose/g) and highest (approximately 1-2% dose/g) in the spleen and lungs. The present findings indicate that the use of [11C]CP 96,345 in PET might be more applicable to the study of substance P receptors in peripheral tissues involved with inflammatory disease and arthritis.
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PMID:Synthesis of a nonpeptide carbon-11 labeled substance P antagonist for PET studies. 768 41

Prolyl endopeptidase, which has long been recognised for its importance in the degradation of several neuropeptides such as thyroliberin, luteinising hormone releasing hormone, angiotensin, substance P and neurotensin, has been widely characterised as a cytosolic enzyme. However, in this paper, we report the presence of a prolyl endopeptidase activity in the particulate fractions of bovine brain, which is distinct from that in the cytoplasm. This previously uncharacterised activity was found to reside in the synaptosomal membranes, a location which is highly significant for the inactivation of neuropeptides in brain. Following vigorous salt washing and osmotic shock, the prolyl endopeptidase activity was released from the membranes by treatment with the detergent Triton X-100, and was partially purified by gel filtration on a Sephacryl S-200HR column. This prolyl endopeptidase activity was shown to have a molecular mass (87 kDa) higher than the cytosolic prolyl endopeptidase but, from initial investigation, appears to demonstrate a similarly broad substrate specificity towards proline-containing neuropeptides. The partially purified enzyme was inhibited by certain thiol-protease inhibitors and was also found to be sensitive to the metal chelator 1,10-phenanthroline.
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PMID:Identification and localisation of a synaptosomal membrane prolyl endopeptidase from bovine brain. 785 96

The present study investigated the effect of the central injection of selective tachykinin (TK) agonists on the need-free intake of 0.9% NaCl in rats. Isotonic NaCl was offered for 60 min (between 1800 and 1900 h); water was offered for 4 h (between 1800 and 2200 h). The TK agonists were injected into the third ventricle just before access to fluids. The NK3-selective agonists [Asp5,6,MePhe8]substance P(5-11) and Succ[Asp6,MePhe8]substance P(6-11), as well as the NK1-selective agonist [Sar9, Met(O2)11]substance P, markedly reduced salt intake, the threshold dose for their effects being 5 ng/rat. The NK2-selective agonist GR64349 reduced salt intake only at 500 ng/rat. At the dose of 31.2 ng/rat, neither the NK1 nor the NK3 agonists inhibited water intake, when water was the only fluid offered (between 1800 and 2200 h), or modified food intake in food-deprived rats. The present study shows that a) TKs inhibit not only the need-induced salt intake, but also the need-free intake of isotonic saline, b) this effect is behaviorally selective, and c) the effect is apparently mediated by NK1 and NK3 receptors. The finding that TKs suppress salt intake in a large variety of experimental conditions supports the idea that the antinatriorexic effect of TKs is independent of the physiological and hormonal status of the animal. It is hypothesized that TKs might modify taste sensitivity or the hedonic evaluation of the salty taste.
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PMID:Inhibition of isotonic sodium chloride intake in the rat by selective tachykinin agonists. 820 81

In addition to altering vascular tone by stimulating primary afferent nerves and acting through reflex pathways, capsaicin acts locally. We examined effects of topically applied capsaicin on arteriolar diameter in striated muscle and tested the hypothesis that capsaicin can alter microvascular tone by releasing substance P (SP) or calcitonin gene-related peptide (CGRP). In anesthetized rats, the right cremaster muscle was exposed and suspended in a tissue bath filled with a physiological salt solution. Diameters of third-order arterioles were displayed and measured using in vivo video microscopy. In 17 of 20 rats, addition of capsaicin (3 x 10(-7) M) to the bath dilated arterioles (85 +/- 14% above control). Failure of a second administration of capsaicin to produce a sustained dilation in 6 of 7 arterioles that had previously dilated to capsaicin is consistent with the hypothesis that this agent causes depletion of an endogenous vasodilator. Pretreatment with an SP inhibitor did not alter capsaicin-induced dilation. CGRP (1 x 10(-10) to 2 x 10(-8) M) caused dilation similar to that caused by capsaicin. Pretreatment with a CGRP inhibitor to the bath prevented capsaicin-induced dilation, but not constriction. These results suggest that capsaicin can dilate microvessels by releasing CGRP, which can modulate tone.
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PMID:Arteriolar dilation mediated by capsaicin and calcitonin gene-related peptide in rats. 823 28

Were studied the peptidergic mechanisms of regulation of the specialized forms of alimentary behaviour, i.e. the "salt" and "carbohydrate appetites", and the control of taste afferentation in the process of sodium chloride and saccharose consumption. Saccharose consumption controlled with participation of cholecystokinin was found to be mediated by an increase of taste afferentation under the influence of this peptide. Specialized sodium chloride consumption is under the control of the peptides litorine and substance P and mediated by a selective intensification of taste afferentation under the influence of these peptides. Active immunization by litorin-albumin and substance P-albumin conjugates was carried out to gain a high level of endogenous antibodies to these peptides. Injections of capsaicin to newborn rats was done for a degeneration of the substance P-containing nerve fibers. The methods used confirmed the specific participation of these peptides in a systemic regulation of salt consumption and activity of the chemoreceptors of the tongue. Were analyzed the main principles of the peptidergic regulation of the specialized forms of alimentary behaviour and the role of chemosensory afferentation in a correction of the process of consumption of the substances.
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PMID:[The peptidergic mechanisms controlling specialized appetites and taste afferentation]. 831 64

The controlling factors of lachrymal gland secretions were examined in the euryhaline turtle, Malaclemys terrapin. Histochemical and immunocytochemical methods were used to localize some of the possible neurotransmitters involved. There was no immunoreactivity to choline acetyltransferase, the enzyme synthesizing acetylcholine, nor did the histochemical technique for acetylcholinesterase produce positive results. Immunofluorescence and immunoperoxidase labels revealed vasoactive intestinal peptide (VIP)- and neuropeptide Y (NPY)-like immunoreactivity in high concentrations surrounding the secretory tubules and ducts. Substance P produced a weak immunoreactivity in the interstitial space surrounding the ducts. Dopamine beta-hydroxylase, the enzyme synthesizing norepinephrine and epinephrine, was localized around the blood vessels. Immunogold labeling confirmed the presence of VIP- and NPY-like reactivity in nerve varicosities close to the basement membrane of the secretory epithelium, and double-labeling showed VIP and NPY are co-localized within the same nerve terminals. The results suggest that the secretory epithelium may be primarily under peptidergic control while the vascular system is under adrenergic control. This is possibly a new pattern of innervation for exocrine glands and may be related to the particular function of this salt gland in an euryhaline turtle.
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PMID:Peptidergic and adrenergic innervation of the lachrymal gland in the euryhaline turtle, Malaclemys terrapin. 857 94

This paper is the first to describe aspects of the mechanics of retching in the insectivore Suncus murinus (house musk shrew) and in an animal of such a small size (approximately 50 g). In anaesthetised animals using the novel stimulus of mechanical stimulation of the upper gastrointestinal tract as the provocative stimulus the frequency of retching was found to be about 4 retches/s, a much higher frequency than in other species (dog, cat, ferret). These studies show that quantification of retching in Suncus cannot be undertaken using direct observation. The temporal pattern of the emetic response was characterised in conscious Suncus using motion (1 Hz, 5 min) and nicotine (20 mg/kg s.c.). The ultrapotent capsaicin analogue resiniferatoxin (100 micrograms/kg s.c.) was discovered to be highly emetic and comparative studies showed that nicotine and resiniferatoxin induced the most intense responses with episodes (retches and a vomit) occurring every 10-15 s. The retching response to mechanical stimulation in the anaesthetised Suncus was not blocked by a 5-HT3 receptor antagonist (granisetron, 1-5 mg/kg s.c.), a tachykinin NK1 receptor antagonist (CP-99,994 20 mg/kg s.c. dihydrochloride salt (9+) -(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine) or morphine (2 mg/kg s.c.) but was blocked by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT 100 micrograms/kg s.c.). Suncus appears to be a suitable animal in which to study the pharmacology of the emetic response to mechanical stimulation of the gut. The results are discussed in the light of studies of the pharmacology of emesis in other species.
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PMID:The pharmacology of the emetic response to upper gastrointestinal tract stimulation in Suncus murinus. 883 19


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