Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human isolated central (5 to 12 mm) and peripheral (< 2 mm) bronchi were contracted with 3 microM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. NG-Nitro-L-arginine (L-NOARG) (10 microM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer D-NOARG was without effect. This inhibition was reversed by L-arginine (1 mM) but not be D-arginine (1 mM). The nitric oxide donor compound, 3-morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, alpha-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving L-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide.
 ...
PMID:Inhibition by L-NG-nitro-L-arginine of nonadrenergic-noncholinergic-mediated relaxations of human isolated central and peripheral airway. 145 72

1. The nature of the non-adrenergic, non-cholinergic (NANC) transmitter was studied in vitro in the rat duodenum, by use of an isometric-isovolumic preparation. 2. Electrical field stimulation (EFS) induced a tetrodotoxin (TTX)-sensitive fall both in luminal pressure and in isometric tension. 3. Neurotensin (NT) induced TTX-insensitive inhibitory responses similar to those induced by EFS. Vasoactive intestinal peptide (VIP) caused a delayed, slow, concentration-dependent, TTX-insensitive inhibitory effect, detected only by a change in luminal pressure. 4. alpha-chymotrypsin prevented the NT- and VIP-induced inhibitory effects and antagonized the response to EFS. 5. Apamin antagonized the EFS- and NT-induced effects, but failed to affect the relaxation in response to exogenous VIP. 6. Desensitization of NT receptors by exposure to NT (10 nM) for 30 min did not affect the EFS-induced relaxation. 7. These findings provide support for the involvement of a peptide in the NANC relaxation in rat duodenum. However, there is no evidence that NT or VIP are neurotransmitters released from the NANC system in this preparation.
 ...
PMID:On the peptidergic hypothesis for non-adrenergic non-cholinergic innervation in the rat duodenum. 158 27

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad range of biological activities in various tissues. After interaction with its membrane receptor, VIP generally induces a very large increase in the intracellular cyclic AMP level. Receptors for VIP have been described in numerous tissues and cell lines. The first results on VIP receptor structure have been obtained by covalent cross-linking using bifunctional reagents. The molecular mass of the different components characterized in this way differs greatly according to the species and the tissue used. This heterogeneity may reflect either a difference in the length of the cross-linked polypeptide backbone or differently glycosylated forms of the same polypeptide. The VIP binding site of intact human adenocarcinoma cells (HT29 cells) is an Mr 64,000 glycoprotein with 20kDa of N-linked oligosaccharide side chains containing sialic acid. The structure of the VIP binding site from HT29 cell is compared, first to the structure of the VIP receptor from other tissues, particularly that from rat liver, and second to the structure of the hepatic glucagon binding site. Recently, solubilization of the VIP receptor in an active form has provided a new way of studying this receptor. The HT29 cell line is an appropriate model to study the dynamics of the VIP receptor. After binding to its receptor, VIP is rapidly internalized, probably by receptor-mediated endocytosis. This internalization leads to a decrease in the cell surface receptor number and simultaneously to a homologous desensitization of adenylate cyclase. VIP is then degraded in the lysosomes, while most of the receptors are recycled back to the cell surface. The presence of an intracellular pool of unoccupied VIP receptors has been demonstrated after inactivation of the cell surface receptors by chymotrypsin. The kinetics of the receptor reappearance at the cell surface, after inactivation by chymotrypsin or after receptor-mediated endocytosis, indicate 2 possible intracellular pathways for occupied and unoccupied VIP receptors.
 ...
PMID:The vasoactive intestinal peptide (VIP) receptor: recent data and hypothesis. 285 63

Vasoactive intestinal peptide (VIP) caused concentration-dependent relaxation in precontracted segments of trachea, hilar bronchus, intrapulmonary bronchus and intrapulmonary artery (IPA) isolated from cat lungs. VIP-induced relaxation responses were abolished by preincubation of tissues with the proteolytic enzyme, alpha-chymotrypsin (2 units ml-1). At the concentration employed, alpha-chymotrypsin treatment did not adversely affect tissue viability as isoprenaline and bethanechol continued to relax airways and IPA, respectively. Aprotinin prevented enzymatic degradation of VIP by alpha-chymotrypsin as demonstrated by the ability of VIP to relax tissues incubated with both the peptidase inhibitor and alpha-chymotrypsin. A spectrum of peptidase inhibitors, including aprotinin, leupeptin, bestatin, bacitracin, beta-phenylpropionic acid and captopril, individually or in combination, did not augment the relaxant effects of VIP in isolated pulmonary tissues. These results suggest that local enzymatic degradation may not be a primary route for inactivation of VIP in cat isolated airways and IPA. If VIP acts as a neurotransmitter in these tissues, a mechanism other than enzymatic proteolysis may be responsible for terminating its action.
 ...
PMID:Relaxation of cat tracheobronchial and pulmonary arterial smooth muscle by vasoactive intestinal peptide: lack of influence by peptidase inhibitors. 614 70

1. We investigated the effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the peptidase alpha-chymotrypsin on non-adrenergic, non-cholinergic (NANC neural) bronchoconstriction induced by electrical stimulation of the vagus nerves and by capsaicin in anaesthetized guinea-pigs in vivo using pulmonary insufflation pressure (PIP) as an index of bronchial tone. We also investigated the contribution of soluble guanylyl cyclase (SGC) to NANC neural relaxant mechanisms. 2. In the presence of atropine and propranolol, electrical stimulation of the vagus nerves induced a frequency-dependent increase in PIP above baseline of 67% at 2.5 Hz, of 128% at 5 Hz and of 230% at 10 Hz. L-NAME (1-50 mg kg-1, i.v.), at doses inducing increases in systemic blood pressure, dose-relatedly potentiated NANC bronchoconstriction. At 10 mg kg-1 i.v., L-NAME significantly (P < 0.05) potentiated NANC bronchoconstriction by a further 106% at 2.5 Hz and a further 147% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. L-NAME did not induce bronchoconstriction in sham-stimulated control animals. D-NAME did not potentiate NANC bronchoconstriction. Raising systemic blood pressure with phenylephrine did not potentiate vagally-induced bronchoconstriction (2.5 Hz). 3. The NO precursor L-arginine, but not D-arginine, (100 mg kg-1, i.v.) significantly reversed the potentiation by L-NAME of NANC bronchoconstriction. L-Arginine alone significantly inhibited neurogenic bronchoconstriction at 10 Hz (by 74%); the inhibition of 25% at 2.5 Hz was not significant. 4. L-NAME did not significantly affect the increases in PIP induced by intravenous substance P. neurokinin A (NKA) or capsaicin. 5. The inhibitor of SGC, methylene blue (10 mg kg', i.v.) potentiated (by 110-140%) NANC neural bronchoconstriction induced by lower frequencies of nerve stimulation and reversed the reduction in PIP induced by the SGC activator, sodium nitroprusside (SNP, 1.05 mg kg- 1, i.v.). SNP significantly (P <0.05) reduced by 65% the bronchoconstriction induced by nerve stimulation at 10 Hz. Methylene blue did not effect baseline PIP in sham-stimulated controls. The airway effects of methylene blue and SNP were not associated with their cardiovascular effects. 6. a-Chymotrypsin (2 units kg-', i.v.) significantly potentiated vagally-induced bronchoconstriction by a further 63% at 2.5 Hz, by a further 95.6% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. alpha-Chymotrypsin also potentiated (by 116%) capsaicin-induced bronchoconstriction. Vasoactive intestinal peptide (VIP, 10 ig kg-' i.v. infused over min) significantly reduced by 70% the increase in PIP induced by NKA (0.1 .Lmol kg-' i.v., infused over 30 s). 7. The combination of a-chymotrypsin (2 units kg-', i.v.) and L-NAME (5 mg kg-', i.v.) significantly potentiated NANC bronchoconstriction by a further 304% at 2.5 Hz, an increase in PIP which was greater than that induced by either a-chymotrypsin or L-NAME alone (P <0.05). 8. We conclude that endogenous NO and a bronchodilator peptide, possibly VIP, released in association with nerve stimulation, as well as activation of soluble guanylyl cyclase, regulate the magnitude of NANC neurogenic bronchoconstriction in guinea-pigs in vivo.
 ...
PMID:Regulation of NANC neural bronchoconstriction in vivo in the guinea-pig: involvement of nitric oxide, vasoactive intestinal peptide and soluble guanylyl cyclase. 767 32

Neurotransmitters mediating nonadrenergic-noncholinergic (NANC) relaxation were investigated in strips of porcine retractor penis muscle (RPM). Muscle tone was raised by phenylephrine (1 microM) in the presence of atropine (1 microM) and guanethidine (50 microM). Upon electrical field stimulation (1 ms, 80 V, 1-32 Hz for 10 s), the initial fast relaxation was followed by the slow relaxation. Although the fast and the slow relaxation were completely abolished by tetrodotoxin (1 microM), they showed different pharmacological sensitivities to the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). The fast relaxation was markedly inhibited by L-NAME in an L-arginine reversible manner and by oxyhemoglobin (50 microM), while the slow relaxation was hardly blocked by L-NAME. L-NAME and alpha-chymotrypsin (alpha-CT, 3 U/ml) selectively inhibited the fast and the slow relaxation, respectively. Alpha-CT abolished L-NAME-resistant slow relaxation, and L-NAME completely abolished the alpha-CT-resistant fast relaxation. Alpha-CT-resistant relaxation was not significantly different from the digitally calculated L-NAME-sensitive component, and L-NAME-resistant relaxation was similar to the digitally calculated alpha-CT-sensitive component. Vasoactive intestinal peptide (VIP, 0.003-0.1 microM) relaxed porcine RPM in a concentration-dependent manner. The effect of a VIP was partially inhibited by a VIP receptor antagonist, VIP(10-28) (1 and 3 microM). L-NAME-resistant relaxation was also reduced by VIP(10-28) (3 microM) and by another putative antagonist, VIP(6-28) (1 microM), although the effects of the two antagonists were somewhat inconsistent. From the histochemical staining, it was verified that nerve bundles that showed VIP-like immunoreactivities were also positive for the NADPH diaphorase reaction. These results suggest that NO and peptide neurotransmitter(s) including VIP mediate the NANC relaxation in porcine RPM.
 ...
PMID:Involvement of nitric oxide and vasoactive intestinal peptide in the nonadrenergic-noncholinergic relaxation of the porcine retractor penis muscle. 1145 27