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)

Electrical field stimulation of 5-hydroxytryptamine contracted cat trachea and bronchi in the presence of cholinergic and adrenergic blockade caused relaxation by activating intrinsic nonadrenergic noncholinergic (NANC) inhibitory nerves. Pretreatment of the tissues with the proteolytic enzyme, alpha-chymotrypsin, did not affect NANC inhibitory responses. Relaxations induced by vasoactive intestinal peptide (VIP) were abolished by alpha-chymotrypsin. These results suggest that VIP or related peptides may not act as the NANC inhibitory transmitter in cat airways. However, the possibility remains that peptides not susceptible to degradation by alpha-chymotrypsin may mediate these NANC inhibitory responses.
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PMID:Effect of alpha-chymotrypsin on the nonadrenergic noncholinergic inhibitory system in cat airways. 404 22

Vasoactive intestinal polypeptide (VIP), located within intrinsic neurones of the guinea-pig taenia coli, has been proposed as a neurotransmitter which may mediate certain non-adrenergic, non-cholinergic effects within the gastrointestinal tract. The relaxation of the taenia coli produced by exogenous VIP has a longer latency and time to maximum than the relaxation which is obtained during electrical stimulation of the non-adrenergic, non-cholinergic nerves. The responses to exogenous VIP (0.03-1 microM) were abolished by the proteolytic enzyme alpha-chymotrypsin (1 U/ml), whereas there were no statistically significant changes in the inhibitory responses to intramural nerve stimulation (0.1-5 Hz) or exogenous ATP (0.03-100 microM), which closely mimics the nerve-mediated response. Apamin is a neurotoxin which prevents the increase in K+ conductance associated with the inhibitory junction potential produced by stimulation of the non-adrenergic, non-cholinergic inhibitory nerves. In the presence of apamin (0.005-1 microM) the responses to intramural nerve stimulation and exogenous ATP were significantly antagonised, and often converted to contractile responses. The VIP-induced relaxations during apamin treatment were not significantly decreased. These results suggest that VIP is unlikely to be the transmitter released from the non-adrenergic, non-cholinergic nerves of the guinea-pig taenia coli, and are consistent with the view that these nerves are purinergic in nature.
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PMID:Evidence against vasoactive intestinal polypeptide being the non-adrenergic, non-cholinergic inhibitory transmitter released from nerves supplying the smooth muscle of the guinea-pig taenia coli. 610 36

We have studied in seven men, consuming less than 50 g alcohol daily, the effect of intravenous (i.v.) ethanol on (a) hormonally (secretin + CCK PZ) submaximally stimulated pancreatic secretion and (b) blood levels of pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and somatostatin. After intravenous ethanol (600 mg/kg), pancreatic secretion decreased in all subjects and plasma levels of PP and VIP increased significantly. Moreover, there was a significant correlation between the mean inhibition of chymotrypsin output and the mean increase in PP plasma levels during the first 45 min following ethanol infusion. Therefore i.v. infusion of alcohol elicits release of PP and VIP and PP release could explain in part at least the alcohol-induced pancreatic inhibition observed in non-alcoholic men.
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PMID:Relationship between intravenous ethanol, alcohol-induced inhibition of pancreatic secretion and plasma concentration of immunoreactive pancreatic polypeptide, vasoactive intestinal peptide, and somatostatin in man. 611 82

The large arteries at the base of the brain in the pig were studied in vitro for their responsiveness to neurogenic and humoral stimuli. Helical strips of these cerebral vessels tonically contracted consistently following application of resting force. The development and maintenance of this tone were not influenced by prior treatment of strips with tetrodotoxin (5 x 10(-7) M), 6-hydroxydopamine (300 micrograms/ml) guanethidine (5 x 10(-6) M), or antagonists of known vasoactive autacoids (i.e., phentolamine, propranolol, atropine). Once tone reached an equilibrated plateau, transmural nerve stimulation and exogenously applied norepinephrine evoked a relaxation. The relative potency of beta-adrenergic agonists in producing a relaxation was isoproterenol greater than norepinephrine greater than epinephrine much greater than terbutaline. The response to norepinephrine, but not that to transmural nerve stimulation, was abolished by beta-adrenoceptor antagonists. The neurogenic response, but not the relaxation to exogenous catecholamines, was blocked by tetrodotoxin and 6-hydroxydopamine and diminished by guanethidine. Vasoactive intestinal polypeptide and adenosine were also potent relaxant agents. These responses, but not the response to transmural nerve stimulation were blocked by alpha-chymotrypsin (1.5 U/ml) and aminophylline (3 x 10(-5) M), respectively. These results suggest that porcine cerebral vessels develop myogenic tone which allows one to examine neural and/or humoral dilator responses without prior spasmogen addition. The vascular beta-receptors appear to be of the beta 1-subtype which is consistent with that found in other species. The nature of the dilator neurotransmitter is unknown, but the functional integrity of the adrenergic nerve terminals appears important for the neurogenic relaxation.
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PMID:Relaxation to transmural nerve stimulation and exogenously added norepinephrine in porcine cerebral vessels. A study utilizing cerebrovascular intrinsic tone. 612 83

1. We have investigated the correlation between relaxation and changes in cyclic nucleotide content of human tracheal smooth muscle (HTSM) in vitro following inhibitory non-adrenergic non-cholinergic (i-NANC) neural bronchodilator responses evoked by electrical field stimulation (EFS), and compared these with changes seen with sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1) and vasoactive intestinal peptide (VIP). The effects of N omega-nitro-L-arginine methyl ester (L-NAME), Methylene Blue and alpha-chymotrypsin (alpha-CT) were studied. 2. EFS (10 Hz, 1 ms, 40 V for 30 s) evoked a time-dependent relaxation accompanied by a concurrent rise in cGMP, both of which were maximal at 30 s and unaffected by epithelium removal. Levels of cAMP were more variable than those of cGMP and were not significantly changed at any time point. 3. SIN-1 (1 mM) and SNP (100 microM) also produced time-dependent relaxations which were maximal between 2 and 8 min, accompanied by concomitant rises in cGMP; however, these changes were larger than those associated with i-NANC relaxations. cAMP levels were unchanged at all time points. 4. EFS-evoked i-NANC relaxations and cGMP increases (time, t = 30 s) were inhibited by L-NAME. The effects were partially reversed by L-arginine (1 mM), but not by D-arginine. D-NAME and alpha-CT (2 u ml-1) had no effect on either relaxation or cGMP accumulation. Tetrodotoxin (TTX, 3 microM) inhibited both relaxation and cGMP accumulation. 5. VIP (1 microM) also produced a time-dependent relaxation associated with a concurrent rise in cAMP levels with no change in cGMP levels. 6. Methylene Blue (10 microM) partially inhibited EFS (10 Hz)-evoked i-NANC relaxation and cGMP accumulation, and almost completely inhibited both relaxation and cGMP accumulation evoked by SIN-1 (1 mM). Methylene Blue had no significant effect on relaxation or cGMP accumulation evoked by SNP (100 microM). 7. Neural i-NANC relaxations in HTSM are associated with a concurrent selective accumulation of cGMP which is unaffected by epithelium removal. This is inhibited in a stereoselective manner by L-NAME and mimicked by SNP and SIN-1; however, cGMP accumulation was greatly increased with SNP and SIN-1 suggesting compartmentalized changes in cGMP content. VIP also caused relaxation associated with an increase of cAMP; however, no evidence was found for VIP being involved in i-NANC relaxation. Hence nitric oxide (NO), or a NO-containing complex, appears to mediate i-NANC responses in human trachea in vitro.
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PMID:Evidence for the involvement of cGMP in neural bronchodilator responses in humal trachea. 765 Jun 19

1. The mediators of non-adrenergic non-cholinergic (NANC) relaxation of the longitudinal muscle of rat proximal, middle and distal colon were examined in vitro. 2. Electrical transmural stimulation (TMS) of proximal, middle and distal segments of rat colon induced NANC relaxations which were inhibited by tetrodotoxin (1 microM), but not by atropine (1 microM) or guanethidine (4 microM). 3. In the proximal colon, L-nitro-arginine (N5-nitroamidino-L-2,5-diaminopentanoic acid) inhibited the TMS-induced NANC relaxation and L-arginine (1 mM) reversed this inhibition. Nitric oxide (0.3-10 microM) induced relaxation of the proximal segment. 4. NANC relaxation of the proximal segments was still evident after desensitization to vasoactive intestinal peptide (VIP). A VIP antagonist (VIP 10-28, 10 microM) had no effect on the TMS-induced NANC relaxation, which was also resistant to alpha-chymotrypsin (2 units ml-1) and a substance P antagonist ([D-Pro2, D-Trp7,9]substance P, 1 microM). 5. In the middle colon, L-nitro-arginine did not inhibit the TMS-induced NANC relaxation in 6 of 9 preparations tested and partially inhibited the relaxation in the other 3 preparations. L-Arginine did not reverse the partial inhibition. 6. Complete desensitization to VIP was not achieved in the middle colon. The VIP antagonist had no effect on the TMS-induced NANC relaxation. After alpha-chymotrypsin treatment of the segment, desensitization of the segments to substance P, or in the presence of the substance P antagonist, the TMS-induced NANC relaxation was augmented. 7. In the distal colon, L-nitro-arginine did not have any significant effect on the TMS-induced relaxation and nitric oxide did not induce relaxation. The VIP antagonist significantly inhibited TMS-induced NANC relaxation. Alpa-Chymotrypsin-treatment of the distal segments resulted in significant inhibition of NANC relaxation. No desensitization to substance P was achieved. Treatment with the substance P antagonist had no effect. 8. These results suggest that nitric oxide is the mediator of the NANC inhibitory response in the proximal region of rat colon; in the middle colon, substance P acts as an excitatory neurotransmitter, antagonizing the NANC relaxation caused by the mediator of the response, which is still uncertain. Our results suggest that that VIP is the most likely candidate as a NANC transmitter in the distal colon.
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PMID:Mediators of nonadrenergic, noncholinergic inhibition in the proximal, middle and distal regions of rat colon. 768 May 92

Although considerable evidence suggests that NO serves as a neurotransmitter in gastrointestinal muscles, it is unlikely to be the only substance involved in enteric inhibitory neurotransmission. Vasoactive intestinal polypeptide (VIP) is known to be expressed by inhibitory motor neurons in the gut, and it appears to be co-localized with nitric oxide synthase (NOS) in a subpopulation of enteric neurons. These data suggest that NO and VIP may be parallel neurotransmitters. Others have suggested that VIP is the primary inhibitory transmitter, and it stimulates production of NO in smooth muscle cells. In this "serial cascade" model NO is a paracrine substance. We performed experiments on circular muscles and cells from the canine proximal colon to further test the idea that NO and VIP are parallel neurotransmitters and to determine the validity of the serial cascade model in these muscles. We found that NO-independent inhibitory effects were unmasked when excitatory and NO-dependent inhibitory responses were blocked. NO-independent inhibitory effects were reduced by alpha-chymotrypsin and blocked by tetrodotoxin. NOS- and VIP-like immunoreactivities were co-localized in enteric neurons and varicose fibers in the circular muscle layer. Similar to several other reports we found no evidence for a constitutive NOS in smooth muscle cells. Several aspects of the serial cascade model were not supported by our results: (i) the electrical and mechanical effects of VIP did not depend upon NO synthesis; (ii) VIP-induced changes in [Ca2+]i did not depend upon NO synthesis; and (iii) VIP did not cause the release of NO from canine colonic muscles. These results are consistent with the hypothesis that NO and VIP are co-transmitters, released in parallel from enteric inhibitory nerves.
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PMID:Relationship between nitric oxide and vasoactive intestinal polypeptide in enteric inhibitory neurotransmission. 787 Feb 87

Furosemide has recently been shown to be effective in inhibiting various indirect challenges in asthmatic patients, but its mode of action is not yet clear. There is some evidence that furosemide has an inhibitory effect on sensory and cholinergic nerves in the airways. We have investigated the effects of furosemide, bumetanide, and nedocromil sodium on inhibitory nonadrenergic, noncholinergic (iNANC) responses in guinea pig trachea in vitro using electrical field stimulation (50 V, 0.5 ms, 2 to 32 Hz for 30 s) and exogenously applied vasoactive intestinal peptide (VIP) or nitroprusside. In the presence of atropine (1 microM), indomethacin (10 microM), and propranolol (1 microM), both furosemide and bumetanide but not nedocromil sodium produced a concentration-dependent inhibition of the iNANC response (maximum inhibition, 31.2 +/- 5.6% with 100 microM furosemide at 16 Hz and 44.2 +/- 4.1% with 10 microM bumetanide at 4 Hz). Furthermore, after pretreatment of the tissues with L-NG-monomethyl arginine (90 microM), alpha-chymotrypsin (2 U/ml), or both, furosemide and bumetanide produced a further inhibition of the iNANC relaxation. Neither loop diuretic had any effect on the concentration-response curves to exogenous VIP (10(-9) to 10(-7) M) or nitroprusside (10(-8) to 10(-6) M). These results indicate that loop diuretics may inhibit nonadrenergic relaxation in guinea pig trachea in vitro by a prejunctional mechanism, probably through inhibition of nerve activation, the exact mechanism of which is still undefined.
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PMID:Furosemide and bumetanide, but not nedocromil sodium, modulate nonadrenergic relaxation in guinea pig trachea in vitro. 811 71

Human airway smooth muscle possesses an inhibitory nonadrenergic noncholinergic neural bronchodilator response mediated by nitric oxide (NO). In guinea pig trachea both endogenous NO and vasoactive intestinal peptide (VIP) modulate cholinergic neural contractile responses. To identify whether endogenous NO or VIP can modulate cholinergic contractile responses in human airways in vitro, we studied the effects of specific NO synthase inhibitors and the peptidase alpha-chymotrypsin on contractile responses evoked by electrical field stimulation (EFS) at three airway levels. Endogenous NO, but not VIP, was shown to inhibit cholinergic contractile responses at all airway levels but this inhibition was predominantly in trachea and main bronchus and less marked in segmental and subsegmental bronchi. To elucidate the mechanism of this modulation we then studied the effects of endogenous NO on acetylcholine (ACh) release evoked by EFS from tracheal smooth muscle strips. We confirmed that release was neural in origin, frequency dependent, and that endogenous NO did not affect ACh release. These findings show that endogenous NO, but not VIP, evoked by EFS can inhibit cholinergic neural responses via functional antagonism of ACh at the airway smooth muscle and that the contribution of this modulation is less marked in lower airways.
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PMID:Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro. 834 13

Tryptase and chymase released from activated mast cells degrade the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) to peptide fragments. We have examined whether nedocromil sodium can modulate the ability of rat activated peritoneal mast cells to degrade 125I-CGRP and 125I-VIP. Mast cell-dependent degradation of both 125I-CGRP and 125I-VIP was observed with compound 48/80 (0.03-1 microgram/ml) and in the case of 125I-VIP with anti-IgE (1-20 micrograms/ml). Nedocromil sodium (10(-6)-10(-4) M) caused significant inhibition of neuropeptide degradation, with the most effective inhibition observed against anti-IgE-induced degradation of 125I-VIP. Nedocromil sodium had no inhibitory effect on the ability of lysed mast cells, bovine trypsin or chymotrypsin to breakdown 125I-VIP. These results suggest that nedocromil sodium inhibits mast cell-dependent degradation of neuropeptides, such as VIP, as a secondary consequence of inhibiting the release of mast cell proteases.
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PMID:The modulation by nedocromil sodium of proteases released from rat peritoneal mast cells capable of degrading vasoactive intestinal peptide and calcitonin gene-related peptide. 839 43


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