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)

Two non-sulfur containing ACE-inhibitors were tested concerning their local effect on experimental dermatitis in ovalbumin-sensitized guinea pigs. Enalaprilat but not cilazaprilat potentiated the ovalbumin-evoked inflammatory response. Furthermore, enalaprilat clearly enhanced the erythema evoked by substance P, whereas cilazaprilat did not. Concerning, the bradykinin-evoked erythema, enalaprilat significantly potentiated the response, whereas cilazaprilat only caused a slight increase. Our results suggest that different affinities for peptidases involved in degradation of inflammatory peptides can explain differences between the pro-inflammatory properties of enalaprilat and cilazaprilat.
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PMID:Effects of cilazaprilat and enalaprilat on experimental dermatitis in guinea pigs. 171 14

In addition to plasma metabolism of substance P (SP) by angiotensin converting enzyme (ACE; EC 3.4.15.1) (less than 1.0 nmol/min/ml), the majority of SP hydrolysis by rat and human plasma was due to dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) (3.15-5.91 nmol/min/ml), which sequentially converted SP to SP(3-11) and SP(5-11). In turn, the SP(5-11) metabolite was rapidly hydrolyzed by rat and human plasma aminopeptidase M (AmM; EC 3.4.11.2) (24.2-25.5 nmol/min/ml). The Km values of SP for DAP IV and of SP(5-11) for AmM ranged from 32.7 to 123 microM. In contrast, neurokinin A (NKA) was resistant to both ACE and DAP IV but was subject to N-terminal hydrolysis by AmM (3.76-10.8 nmol/min/ml; Km = 90.7 microM). These data demonstrate differential processing of SP and NKA by specific peptidases in rat and human plasma.
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PMID:Differential processing of substance P and neurokinin A by plasma dipeptidyl(amino)peptidase IV, aminopeptidase M and angiotensin converting enzyme. 172 23

1. Cytoplasmic Ca2+ ([Ca2+]i) responses were studied in guinea-pig pancreatic acinar cells during stimulation with cholecystokinin octapeptide (CCK-8), substance P (SP) and carbachol. 2. Individual cells exhibited [Ca2+]i responses to all three agonists. 3. In the absence of external Ca2+, all the agonists initiated [Ca2+]i peaks which, particularly at high agonist concentrations, rapidly declined. 4. SP induced repetitive monophasic [Ca2+]i transients which started from basal [Ca2+]i even after elevation of the external Ca2+ concentration. 5. CCK-8 triggered similar oscillations, which particularly at high agonist concentration or after elevating external Ca2+ became superimposed upon a sustained elevation of [Ca2+]i. 6. Carbachol-induced oscillations were more complex with [Ca2+]i transients superimposed on slower waves. 7. At high carbachol concentrations or elevation of external Ca2+ the slow waves fused into a sustained increase of [Ca2+]i. 8. The protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate attenuated the agonist-induced [Ca2+]i responses, and this effect was reversed by the PKC activator staurosporine. 9. The results indicate that oscillations of [Ca2+]i induced by SP, CCK-8 and carbachol involve intracellular mobilization of Ca2+. 10. CCK-8 and carbachol also cause a rise of [Ca2+]i by a mechanism more directly dependent on the presence of extracellular Ca2+. 11. In the case of carbachol the latter component is subject to oscillatory control. 12. The transition from oscillatory [Ca2+]i to sustained increase may be associated with inhibition of amylase release.
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PMID:Calcium oscillations in guinea-pig pancreatic acinar cells exposed to carbachol, cholecystokinin and substance P. 172 99

A primary culture of the canine jejunal submucosa has been established and used to investigate neuronal somatostatin release. Immunocytochemical characterization of the cultures demonstrated the presence of the following peptidergic neurons: neurotensin (30%), somatostatin (27%), vasoactive intestinal polypeptide (14%), neuropeptide Y (10%), and substance P (5%). No immunoreactive neurons were observed with the available antisera to galanin, gastrin-releasing peptide, and motilin. The concentration of somatostatin-like immunoreactivity, as determined by radioimmunoassay of cell extracts, was 358 +/- 105 pmol/well. Basal release of somatostatin was 4.4 +/- 0.9% total cell content and was significantly inhibited by the addition of substance P at 1 and 100 nM. The addition of the calcium ionophore, A23187, with phorbol 12-myristate 13-acetate stimulated somatostatin release in a concentration-dependent manner. These data indicate that short-term cultures of the jejunal submucosal plexus will be an excellent model for determination of the factors influencing the release of neural somatostatin.
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PMID:Canine jejunal submucosa cultures: characterization and release of neural somatostatin. 197 28

Since 1984 25 cases of enalapril induced angioedema have been reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs. Two patients with enalapril induced angioedema are described. The pathophysiological mechanism of this potentially life-threatening adverse effect is probably not a direct allergic response to the drug itself. Enalapril inhibits angiotensin converting enzyme, which not only metabolizes angiotensin I but also bradykinin and 'substance P'. Bradykinin and 'substance PH may then accumulate and cause angioedema in a direct or indirect way. It is of great importance that instances of oropharyngeal swelling are considered a possible result of an adverse reaction to ACE-inhibitors.
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PMID:[Angioedema caused by enalapril]. 200 23

We investigated effects of various agents on proliferation, intracellular pH (pHi), and intracellular calcium [( Ca2+]i) of rat mesangial cells (MCs) in early passages (2-5). Serum-starved MCs incubated in HCO3- were exposed to one of the following: fetal calf serum (FCS), serotonin, angiotensin II (ANG II), arginine vasopressin (AVP), bombesin (Bom), bradykinin (BK), epidermal growth factor (EGF), epinephrine (Epi), interleukin 1 (IL-1), norepinephrine (NE), neuropeptide Y, oxytocin, substance P (SP), platelet-derived growth factor, or 12-O-tetradecanoylphorbol-13-acetate (TPA). We assessed DNA synthesis from [3H]thymidine uptake during exposure to test agent. All agents except ANG II, NE, Bom, and SP were mitogenic. When MCs were incubated in a HCO3(-) -free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered medium, maximal mitogenic responses to FCS, AVP, and EGF were 41, 44, and 55% (P less than 0.01) lower, respectively, than those in presence of HCO3-. In absence of HCO3-, agents other than BK and IL-1 produced a biphasic pHi response characterized by a transient acidification followed by a prolonged alkalinization that was both Na(+)-dependent and amiloride-sensitive. In presence of HCO3-, agents produced only a small and gradual acidification, except for IL-1 and Epi. Addition of all agonists except IL-1, EGF, and TPA produced significant transient increases in [Ca2+]i, the magnitudes of which were similar in HCO3- and non-HCO3- buffers. These results demonstrate that, in presence of HCO3-, agents (i.e., NE and ANG II) can produce typical [Ca2+]i transients and still not cause MC proliferation. Conversely, an agent may cause proliferation without eliciting a short-term change in either [Ca2+]i or pHi (i.e., IL-1), a change in [Ca2+]i but not pHi (i.e., Epi), or a change in pHi but not [Ca2+]i (i.e., TPA). Thus, at least for MCs, proliferation in HCO3- can be dissociated from early agonist-induced changes in pHi and [Ca2+]i.
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PMID:Effects of mitogens and other agents on rat mesangial cell proliferation, pH, and Ca2+. 211 98

Conditions were established to stimulate human gingival fibroblast explant cultures to synthesize milligram quantities of the metalloproteinase proenzymes, prostromelysin and procollagenase. To stimulate enzyme production, cells were treated with 1 nM recombinant human IL-1 beta for approximately 7 days under serum free conditions. Using a combination of rapid column chromatography steps, approximately 10 milligrams of prostromelysin and 5 milligrams of procollagenase were purified from 1 liter of conditioned media. Prostromelysin electrophoresed as a doublet with molecular weights of 55,57 kD, whereas, procollagenase migrated with slightly lower molecular weights of 52, 54 kD. Both proenzymes were treated with trypsin or aminophenylmercuric acetate to generate active species. The molecular weights of the active enzymes were approximately 10 kD smaller than the proenzymes. Active enzymes were inhibited by metal chelators and the natural metalloproteinase inhibitor, tissue inhibitor of metalloproteinase (TIMP), but not by the serine protease inhibitor, phenylmethylsulfonyl fluoride (PMSF). Activated stromelysin degraded a number of substrates including transferrin, proteoglycan monomer, proteoglycan aggregated with hyaluronic acid, and substance P. By contrast, collagenase degraded interstitial type I collagen and the peptide thioester, Ac-Pro-Leu-Gly-SCH(iBu)Co-Leu-GlyOEt. Identity of both enzymes were confirmed by amino-terminal protein sequence analysis as well as by immunoblot analysis using monoclonal antibodies.
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PMID:Production and purification of prostromelysin and procollagenase from IL-1 beta-stimulated human gingival fibroblasts. 217 90

[(Octahydro-2-oxo-7-tetradecylidene-2H-1-benzopyran-8-yl)thio]acet ic acid (MDL 43,291) is a novel leukotriene (LT) receptor antagonist. It is a competitive antagonist of LTD4 (pA2 = 6.7) and LTE4 (pA2 = 6.7) and an apparent noncompetitive inhibitor of LTC4 ('pseudo' pA2 = 6.8) in the longitudinal muscle of the guinea pig ileum. At concentrations that effectively antagonize peptidoleukotriene-induced contractions, MDL 43,291 does not antagonize histamine, carbachol or substance P. In vivo, 10-30 mg/kg MDL 43,291, given intravenously, effectively inhibits increases in insufflation pressure induced by 100 ng/kg i.v. LTD4. This compound is a prototype of a novel class of leukotriene receptor antagonists that may be useful in the treatment of bronchial asthma and related disorders.
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PMID:Conformationally restricted leukotriene receptor antagonists: [(octahydro-2-oxo-7-tetradecylidene-2H-1-benzopyran-8-yl)thio]ace tic acids. 217 2

1. Effects of inhibition of angiotensin converting enzyme (ACE, EC 3.4.15.1) in brain on psychomotor, exploratory, stereotyped and cognitive behaviour in rats were investigated. To inhibit brain ACE captopril (D-3-mercaptopropanoyl-L-proline) was given orally (p.o., 50 mg/kg) or intracerebroventricularly (i.c.v., 5 micrograms/rat). 3. Captopril given p.o. but not i.c.v. significantly enhanced stereotypy, overall number of conditioned avoidance responses, and decreased blood pressure. 4. No statistically significant influence of captopril given by either route on the number of crossings, rearings and bar approaches in the open field, performance of passive avoidance and number of correct choices as well as the speed of running for food in the T-maze was observed. 5. In conclusion, a small decrease of the activity of nigrostriatal dopaminergic system caused by the decrease of AII and/or increase of bradykinin, substance P, enkephalins and neurotensin in brain resulting from ACE inhibition is postulated.
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PMID:Some behavioural effects of captopril in rats. 227 85

Sodium-replete pigeons drink excess 3% NaCl following concurrent treatment with both i.m. deoxycorticosterone acetate and pulse i.c.v. (p.i.c.v.) angiotensin II. This is not just a consequence of the water intake induced by p.i.c.v. angiotensin II, since the tachykinin eledoisin, given at equidipsogenic dose, does not evoke intake of salt. On the other hand, salt intake is not aroused in the sodium replete pigeon by continuous i.c.v. (c.i.c.v.) infusion of hyperosmotic mannitol (0.7 M) and c.i.c.v. infusions of hyperosmotic NaCl (0.3 M) or mannitol have no effect on the salt intake of the sodium deplete pigeon, or have effects that are unrelated to brain sodium. The salt appetite of the pigeon, like that of the rat, is evoked by an angiotensin and aldosterone synergy, and the angiotensin/aldosterone mechanism may be the general vertebrate theme of this behavior.
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PMID:Angiotensin/aldosterone synergy governs the salt appetite of the pigeon. 236 14


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