Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of capsaicin and neuropeptides were examined in equine tracheal smooth muscle (TSM). Neither capsaicin nor substance P (SP) contracted TSM. Capsaicin (100 microM) elicited relaxation in TSM contracted with methacholine. This relaxation was not mimicked by SP or calcitonin gene-related peptide (CGRP). Relaxation was not attenuated by removal of the epithelium or by pretreatment of tissue with meclofenamate or the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine. Previous exposure of TSM to capsaicin did not eliminate the relaxation responses to subsequent capsaicin. Although vasoactive intestinal peptide (VIP) elicited marked relaxation that was attenuated by alpha-chymotrypsin, alpha-chymotrypsin did not affect the capsaicin-induced relaxation. Capsaicin-induced relaxation was abolished by charybdotoxin, a blocker of large-conductance Ca(2+)-activated K+ channels. These results indicate that capsaicin-induced equine TSM relaxation is not mediated either by neuropeptides such as SP or CGRP released from capsaicin-sensitive sensory nerves or by prostanoids, NO, or VIP. Relaxation is due to the effect of capsaicin on large-conductance Ca(2+)-activated K+ channels. The peptidergic nerves play no important role in the regulation of TSM tone in horse airways.
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PMID:Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle. 937 26

Dopexamine is a synthetic catecholamine used for the management of low-cardiac-output states. The purpose of this study was to characterize some of the mechanisms underlying dopexamine-mediated relaxation in the guinea pig pulmonary artery (PA) in vitro. Dopexamine (EC50, 1.2 microM; Rmax, 100%), like dobutamine (EC50, 1.4 microM, Rmax, 93.3%), prostacyclin (PGI2; EC50, 37 nM; Rmax, 96.2%), sodium nitroprusside (EC50, 370 pM; Rmax, 96.9%), forskolin (EC50, 47 pM: Rmax, 98.6%), and SKF 38393 (EC50, 120 nM; Rmax, 100%), caused graded relaxation in rings of PA precontracted by phenylephrine. The dopexamine vasorelaxation was antagonized by propranolol (1 microM), SCH 23390 (100 nM, a D1-dopamine antagonist), sulpiride (1 microM), glibenclamide (30 microM), tetraethylammonium (3 mM), apamin (100 nM), charybdotoxin (100 nM), SQ 22536 (10 microM, an adenylyl cyclase inhibitor), KT 5720 (10 microM, a protein kinase A inhibitor) and by calcitonin gene-related peptide (CGRP) or vasoactive intestinal peptide (VIP)-receptor antagonists (both 100 nM), as well as by chymotrypsin (1 U/ml). Neither the prior incubation of N(G)-nitro-L-arginine (100 pM), indomethacin (1 microM), nor removal of the vascular endothelium interfered with dopexamine vasorelaxation response in PA. Thus dopexamine relaxation in PA is mediated by activation of beta-adrenoceptors and dopamine receptors, and by the opening of both low- and high-conductance Ca2+-activated K+ channels, partially through adenosine triphosphate (ATP)-sensitive K+ channels. In addition, dopexamine-induced relaxation in PA seems to involve the release of peptides such as VIP and CGRP, an effect mediated by a cyclic adenosine monophosphate (cAMP)-dependent mechanism.
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PMID:Characterization of the mechanism involved in the relaxant response of dopexamine in the guinea pig pulmonary artery in vitro. 989 Apr 1

Stimulation of capsaicin sensitive nerves or administration of calcitonin gene-related peptide (CGRP) before induction of acute pancreatitis (AP) attenuates pancreatic damage, whereas CGRP administration after development of AP aggravates lesion of pancreatic tissue. The aim of this study was to determine the effect of prolonged activity of sensory nerves or CGRP administration on the pancreatic repair after repeated episodes of AP. Five episodes of acute caerulein-induced pancreatitis (10 microg/kg/h for 5 h s.c.) were performed at weekly intervals in rats receiving either vehicle or capsaicin at the sensory nerve stimulatory dose (0.5 mg/kg, 3 times daily), or CGRP (10 microg/kg, 3 times daily). Two weeks after the last induction of AP morphological signs of pancreatic damage, pancreatic blood flow (PBF), serum and pancreatic amylase activity, fecal chymotrypsin activity, pancreatic weight, pancreatic RNA and DNA content, as well as, serum interleukin-1beta (Il-1beta ) were assessed. Pancreata of animals receiving vehicle alone showed almost full recovery within two weeks after last episode of pancreatitis induction. In capsaicin-treated group of rats, we observed the increase in PBF by 44% and in serum Il-1beta concentration by 91%. The pancreatic amylase activity, fecal activity of chymotrypsin, pancreatic nucleic acids content and DNA synthesis were decreased. In rats treated with CGRP the alterations in PBF, serum Il-1beta concentration, as well as, in pancreatic and fecal activity of enzymes were similar to capsaicin treated group but less pronounced. We conclude that prolonged activity of capsaicin-sensitive sensory nerves and the presence of their main mediator-CGRP during pancreatic regeneration after AP leads to pancreatic functional insufficiency typical for chronic pancreatitis.
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PMID:The influence of sensory nerves and CGRP on the pancreatic regeneration after repeated episodes of acute pancreatitis in rats. 1101 64

The function of primary sensory neurons is to receive and transmit information from external environment and these neurons are able to release neuromediators from the activated peripheral endings. The aim of this study was to determine the influence of sensory nerves and administration of their mediator--calcitonin gene related peptide (CGRP) on the course of acute pancreatitis (AP). Ablation of sensory nerves was performed by neurotoxic dose of capsaicin (100 mg/kg). Single or repeated episodes of AP were induced by caerulein infusion (10 microg/kg/h for 5 h). Five repeated AP were performed once a week. Capsaicin at the dose which stimulates sensory nerves (0.5 mg/kg/dose) or CGRP (10 microg/kg/dose) was administrated before and during or after single induction of AP, as well as, after each induction of repeated AP. Rats were killed at the time 0, 3 or 9 h after single induction of AP or two weeks after last induction of repeated AP. Ablation of sensory nerves aggravated pancreatic damage in caerulein-induced AP. Treatment with stimulatory doses of capsaicin or CGRP before and during single induction of AP attenuated the pancreatic damage in morphological examination. This effect was also manifested by partial reversion of AP evoked drop in DNA synthesis and pancreatic blood flow (PBF). Administration of CGRP after single AP induction aggravated histologically manifested pancreatic damage. The further decrease in PBF and DNA synthesis was also observed. Animals with five episodes of AP showed almost full pancreatic recovery two weeks after last induction of AP concerning all parameters tested. In stimulatory doses of capsaicin treated rats, we observed the decrease in pancreatic amylase and fecal chymotrypsin activity, as well as, the drop in DNA synthesis. Similar but less pronounced effects were observed after treatment with CGRP. We conclude that effect of sensory nerves and CGRP on AP is two-phase and time dependent. Stimulation of sensory nerves or the administration of CGRP during development of AP exhibits protective effects against pancreatic damage induced by caerulein overstimulation. After induction of AP, persistent activity of sensory nerves and presence of CGRP aggravate pancreatic damage and lead to functional insufficiency typical for chronic pancreatitis.
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PMID:Effect of sensory nerves and CGRP on the development of caerulein-induced pancreatitis and pancreatic recovery. 1178 67

The oral bioavailability of salmon calcitonin is strongly reduced due to the enzymatic degradation by luminally secreted serine proteases. Apart from being degraded by trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1), it was shown in this study that calcitonin is also digested by elastase (EC 3.4.21.36). It was therefore the aim of this study to generate polymeric excipients protecting perorally administered salmon calcitonin from degradation by these enzymes. Mediated by a carbodiimide trypsin and chymotrypsin inhibitor Bowman-Birk inhibitor (BBI) and elastase inhibitor elastatinal were each covalently attached to the mucoadhesive polymer chitosan. The share of the Bowman-Birk inhibitor in the resulting conjugate was 3.5+/-0.1% (w/w, mean+/-S.D., n=4) and that of elastatinal 0.5+/-0.03% (w/w, mean+/-S.D., n=4). Enzyme assays with synthetic substrates demonstrated a strong inhibitory effect of the chitosan-BBI conjugate towards trypsin and chymotrypsin as well as of the chitosan-elastatinal conjugate towards elastase. In an artificial intestinal fluid containing physiological concentrations of trypsin, alpha-chymotrypsin and elastase, calcitonin being incorporated in unmodified chitosan (0.5%, w/v) was degraded by 99.7+/-0.1% (mean+/-S.D., n=3) within 2h at 37 degrees C. On the contrary, incorporating the drug in chitosan-BBI conjugate and chitosan-elastatinal conjugate (1+1, 0.5%, w/v) led to a degradation of only 36.4+/-0.9% (mean+/-S.D., n=3). Hence, the chitosan-inhibitor conjugates described in this study seem to be promising tools for the oral delivery of salmon calcitonin.
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PMID:In vitro evaluation of polymeric excipients protecting calcitonin against degradation by intestinal serine proteases. 1255 Jul 94

The current work compared protective effects of various ovomucoid species against salmon calcitonin (sCT) metabolism by serine proteases. sCT solutions (50 microM) were incubated at 37 degrees C with trypsin (0.5 microM), alpha-chymotrypsin (0.1 microM), or elastase (0.48 microM) in 50 mM Tris buffer (pH 8.0) containing or lacking different concentrations of turkey ovomucoid (tOVM), duck ovomucoid (dOVM), or chicken ovomucoid (cOVM) and aprotinin. Caco-2 cell homogenate was also incubated with sCT and the contents of the proteases were assayed by using their specific substrates. Metabolites were identified by high-performance liquid chromatography, gel electrophoresis, and matrix-assisted laser desorption ionization mass spectrometry techniques. In the absence of inhibitors, there was a considerable degradation of sCT by the proteases. dOVM and tOVM increased the half-life of sCT with trypsin and alpha-chymotrypsin at enzyme-to-inhibitor ratio of 1:4 showing similar efficacy. dOVM was found to be superior to tOVM in protecting sCT from elastase. cOVM was ineffective in protecting sCT against alpha-chymotrypsin. Caco-2 cell homogenate degraded sCT, which was prevented by tOVM. sCT was cleaved into different molecular weight fragments with different proteases. In general, the metabolite formation decreased when inhibitor concentration increased. dOVM and tOVM effectively stabilized sCT against all three proteases. However, cOVM could not prevent the degradation by alpha-chymotrypsin.
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PMID:Protection of salmon calcitonin breakdown with serine proteases by various ovomucoid species for oral drug delivery. 1470 96

The present study was designed to characterize the urinary bladder-derived relaxant factor that was demonstrated by acetylcholine-induced relaxation response in a coaxial bioassay system consisting of rat bladder as the donor organ and rat anococcygeus muscle as the assay tissue. The concentration-dependent relaxation to acetylcholine (10 nM-1 mM) was inhibited by atropine but was not altered by the antagonists of calcitonin gene-related peptide (CGRP 8-37), vasoactive intestinal peptide (VIP 6-28), tachykinin NK1 (L-732138), tachykinin NK2 (MEN-10376), tachykinin NK3 (SB-218795), purinergic P2 (PPADS) and adenosine (CGS 15943) receptors as well as alpha-chymotrypsin. Adenylate cyclase inhibitor SQ-22536 and protein kinase A inhibitor KT-5720 significantly inhibited the acetylcholine response while guanylate cyclase inhibitor ODQ, and protein kinase C inhibitor H-7 did not have any effect. The P2X agonist alpha,beta-methylene ATP (10 nM-0.1 mM) also produced concentration-dependent relaxation response that was inhibited by PPADS, SQ-22536 and KT-5720 in the coaxial bioassay system. In bladder strips, acetylcholine and alpha,beta-methylene ATP elicited concentration-dependent contractions that were not altered in the presence of SQ-22536 and KT-5720. In conclusion, the urinary bladder-derived relaxant factor that was recognized by the coaxial bioassay system is neither a peptide of the bladder neurons nor a purinergic mediator but adenylate cyclase and protein kinase A are involved in its release and/or relaxant effect. Furthermore, activation of purinergic P2X receptors besides the muscarinic receptors leads to the release of this factor.
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PMID:Rat urinary bladder-derived relaxant factor: studies on its nature and release by coaxial bioassay system. 1862 Oct 43

We found that beta-lactotensin (His-Ile-Arg-Leu), which has been isolated as an ileum-contracting peptide from chymotrypsin digest of bovine beta-lactoglobulin, dose-dependently suppresses food intake after intracerebroventricular (i.c.v.) or intraperitoneal administration at a dose of 40 nmol/mouse or 100mg/kg, respectively, in fasted mice. Orally administered beta-lactotensin also suppressed food intake at 500 mg/kg. We previously reported that beta-lactotensin acts as an agonist for neurotensin receptors; however, the anorexigenic activity of beta-lactotensin was not inhibited by i.c.v. co-administration with SR48692 or levocabastine, an antagonist for neurotensin NT(1) or NT(2) receptor, respectively. On the other hand, the anorexigenic effect of beta-lactotensin was blocked by i.c.v. co-administration with astressin or calcitonin gene-related peptide (CGRP)(8-37), an antagonist for corticotropin releasing factor (CRF) or CGRP, respectively. beta-Lactotensin had affinity for neither CRF nor CGRP receptor. In addition, CRF-induced anorexigenic activity after i.c.v. administration was completely blocked by CGRP(8-37), while CGRP-induced anorexigenic activity was not inhibited by astressin. These results suggest that the CGRP system is activated downstream of the CRF system in food intake regulation. Taken together, beta-lactotensin may suppress food intake by activating the CRF system followed by the CGRP system, independently of the neurotensin system.
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PMID:beta-Lactotensin derived from bovine beta-lactoglobulin suppresses food intake via the CRF system followed by the CGRP system in mice. 1972 Jan 2


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