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 aim of the present study was to investigate the short-term (8-day) effects of feeding a raw soybean diet on exocrine pancreatic secretion and the plasma levels of gastrointestinal hormones in pigs. After adaptation to a heated soybean diet, 6 pigs (36.5 +/- 0.8 kg) were fitted with permanent fistulae of the pancreatic duct, the duodenum and a carotid artery. After post-surgical recovery of 8 days, the animals were submitted to two experimental periods, a 4-day period during which they were fed the heated soybean diet and an 8-day period during which they received the raw soybean diet. Exocrine pancreatic secretion and plasma levels of secretin, cholecystokinin, VIP, PP, somatostatin and gastrin were monitored each day of the two experimental periods. On the first day of raw soybean ingestion and till its end, the daily volume of pancreatic juice was higher than the mean volume measured during heated soybean ingestion. On the contrary, daily total protein output was unchanged. Specific activities of chymotrypsin, amylase and lipase were not modified by the raw soybean diet whereas, from the third day of the experimental period, that of trypsin was higher than the corresponding mean value determined during the first experimental period. Plasma levels of secretin and VIP were higher throughout raw soybean ingestion than the corresponding mean levels determined during the first experimental period. The plasma level of cholecystokinin increased only slightly and in the first days of the second experimental period only. The other gastrointestinal hormones studied were slightly (gastrin) or not (somatostatin, PP) affected by raw soybean feeding. It is suggested that feedback control of exocrine pancreatic secretion in pigs was the mechanism involved in the increase of pancreatic juice observed when raw soybean was fed. This volume increase would result from secretin release into the blood.
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PMID:Short-term (8-day) effects of a raw soybean diet on exocrine pancreatic secretion and plasma gastrointestinal hormone levels in the pig. 371 92

Electrical field stimulation of the isolated pig bladder neck preparation initiated rapid non-adrenergic, non-cholinergic nerve-mediated relaxations. A wide range of substances were examined as possible candidates for the neurotransmitter involved. Of these, only 5-hydroxytryptamine, vasoactive intestinal polypeptide, adenosine and adenosine 5'-triphosphate produced relaxations. Noradrenaline, acetylcholine, substance P, bradykinin and angiotensin II caused contraction, while neurotensin, somatostatin, bombesin and gamma-amino butyric acid were without effect. The nerve response was not blocked by methysergide, ketanserin, chymotrypsin, apamin or 8-phenyltheophylline, although methysergide antagonised the responses to 5-hydroxytryptamine, chymotrypsin blocked the responses to VIP, and 8-phenyltheophylline antagonised the responses to adenosine and ATP.
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PMID:A novel non-adrenergic, non-cholinergic nerve-mediated relaxation of the pig bladder neck: an examination of possible neurotransmitter candidates. 614 1

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.
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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

1. Relaxations of strips of rat gastric fundus were elicited with nicotine (100 mumol/L), nitric oxide (NO; 30 mumol/L), sodium nitroprusside (SNP; 100 nmol/L) and vasoactive intestinal polypeptide (VIP; 1 nmol/L). 2. Methylene blue (30 mumol/L), an inhibitor of soluble guanylate cyclase, reduced relaxations elicited by NO and nicotine, but not those elicited by VIP. 3. Chymotrypsin (1 U/mL) abolished VIP-induced relaxations and reduced nicotine-induced relaxations, but had no effect on SNP-induced relaxations. 4. NG-nitro-L-arginine methyl ester (L-NAME; 100 mumol/L), an inhibitor of NO synthase, reduced relaxations elicited by nicotine, but not those elicited by SNP or VIP. 5. When nicotine-induced relaxations had been reduced by either L-NAME or chymotrypsin, the addition of the other agent produced a greater reduction. However, the relaxations were not abolished. 6. Nicotine-induced relaxations were abolished by tetrodotoxin (1 mumol/L) or hexamethonium (100 mumol/L), indicating that they were due to activation of neuronal nicotinic receptors. Their reduction by methylene blue and L-NAME indicates that an NO-like mediator was involved. Their reduction by chymotrypsin indicates that a VIP-like peptide was involved. However, since they were not abolished by a combination of L-NAME and chymotrypsin, it appears that at least one more as yet unidentified mediator may be involved.
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PMID:Mediators of nicotine-induced relaxations of the rat gastric fundus. 833 69

Non-adrenergic, non-cholinergic (NANC) nerve stimulation results in excitation (e.j.p., rebound depolarization, contractions) or inhibition (i.j.p., afterhyperpolarization, relaxations) of the gut. NANC neuronal mechanisms participate in the maintenance of the basal tone and spontaneous activity of the gut. There are however species differences, i.e. both NANC excitation and inhibition are present in the guinea pig and only NANC inhibition in the rat intestine. Substance P-like neuropeptide/s are suggested to be mediators released from excitatory NANC and sensory nerves. The latter are activated by histamine and degenerated by capsaicin. There is evidence in favor of a nitric oxide-like substance rather than ATP, dopamine, GABA and neuropeptides (e.g. VIP, PHI/PHM) as the inhibitory NANC mediator in the gut. TTX, high Mg(2+)-low Ca2+ media, 3,4-diaminopyridine, dipyridamol and adenosine deaminase modulate NANC excitation and inhibition. The NANC excitation is more sensitive than the NANC inhibition to the action of catecholamines, reserpine, 6-hydroxydopamine, chymotrypsin, prednisolon, bacitracin, opioids, free oxygen species and low concentration of local anesthetics.
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PMID:NANC transmission in intestines and its pharmacological modulation. 839 Nov 98

Smooth muscle cells distributed in the visceral organs are under the control of the autonomic nervous system, and contraction or relaxation of the muscle cells plays an important physiological role in the control of blood pressure, motility of the digestive, respiratory and urinary tracts and secretion. Recent physiological, pharmacological and histochemical investigations indicate that neurotransmitters other than acetylcholine or noradrenaline are involved in peripheral autonomic neuro-effector transmission, and these neurotransmitters are generally termed non-adrenergic, non-cholinergic (NANC) neurotransmitters. The neurotransmitters responsible for excitatory and inhibitory NANC neurotransmission (e-NANC and i-NANC respectively) have not been conclusively identified, but ATP, nitric oxide (NO) and peptides such as VIP and substance P are candidates for these roles. In this review, we discuss the possible role of ATP and NO as e- or i-NANC neurotransmitter in the digestive, respiratory and urinary tracts. Much of the work on NANC innervation in the digestive tract has been carried out on the circular muscle layers of the ileum. This receives inhibitory NANC innervation with ATP responsible for fast relaxation and VIP, and possibly NO, for the slow response. Early and late excitatory junction potentials can be recorded in the presence of atropine. The second is due to substance P since it is blocked in the presence of spantide and by desensitization of the tissue with high doses of substance P. The transmitter responsible for the early NANC contraction has not been identified. Electrical field stimulation (EFS) applied to the tracheal smooth muscle during contraction induced by 5-HT in the presence of atropine and guanethidine elicited monophasic NANC relaxation. By contrast, NANC relaxation elicited in the smaller airways was biphasic, comprising an initial fast component followed by a second slow one. L-NAME selectively abolished the first component without affecting the second. VIP-antagonists or alpha-chymotrypsin considerably attenuated the amplitude of the L-NAME insensitive relaxation. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission in the airway. In the urinary bladder a large, transient atropine resistant contraction occurs in response to pelvic nerve stimulation. This is blocked by alpha, beta methylene ATP suggesting that it is due to ATP. There is no evidence of inhibitory innervation. In the urethra contraction is completely blocked by atropine and guanethidine; a rapid NANC relaxation is abolished by drugs that block NO synthesis. Nerves containing peptides supply both urethra and bladder and may also be involved. These results suggest that all visceral smooth muscles may receive inhibitory NANC innervation involving NO. ATP produces contraction of the urinary bladder but relaxation of the digestive tract. The role of peptides is not yet clear but there is evidence that substance P may be an excitatory transmitter and VIP an inhibitory transmitter in many organs.
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PMID:[The control of smooth muscle tissues by nonadrenergic noncholinergic (NANC) nerve fibres in the autonomic nervous system]. 856 58

1. The effect of 8-week streptozotocin-induced diabetes has been examined on relaxations to non-adrenergic, non-cholinergic (NANC) nerve stimulation in longitudinal strips of rat gastric fundus. 2. In the presence of noradrenergic and cholinergic blockade and raised tissue tone, electrical field stimulation (0.5-4 Hz, 30 s trains) induced frequency-dependent relaxations that were significantly smaller in gastric fundus strips from diabetic rats than in strips from control rats. 3. NG-nitro-L-arginine methyl ester (NAME, 100 microM) significantly reduced NANC relaxations in muscle strips from both control and diabetic rats, but the reduction was greater in muscle strips from diabetic rats than in those from control rats at frequencies of 2 and 4 Hz. alpha-Chymotrypsin (1 u ml-1) slightly reduced relaxations to nerve stimulation in muscle strips from both control and diabetic rats. 4. The duration of NANC nerve relaxations (1-4 Hz, 30 s trains) was smaller in muscle strips from diabetic rats than in those from control rats. The duration of NANC relaxations was reduced by alpha-chymotrypsin (1 u ml-1) in muscle strips from control rats but not in muscle strips from diabetic rats. 5. Relaxations to both nitric oxide (NO; 1-30 microM) and vasoactive intestinal polypeptide (VIP; 0.1-30 microM) were concentration-dependent and did not differ between muscle strips from control and diabetic rats. 6. The results suggest that streptozotocin-induced diabetes impairs relaxations to NANC nerve stimulation in the rat gastric fundus, which are largely mediated by NO and to a lesser extent by VIP. The impairment appears to occur at the prejunctional level, as smooth muscle reactivity to NO and VIP is not altered.
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PMID:Effect of diabetes on relaxations to non-adrenergic, non-cholinergic nerve stimulation in longitudinal muscle of the rat gastric fundus. 856 18

1. To investigate the distribution profile of functional inhibitory non-adrenergic non-cholinergic (i-NANC) nerves and the contribution of NO to the NANC relaxation in the cat, we studied the effects of N omega-nitro-L-arginine methyl ester (L-NAME) on NANC relaxation elicited by electrical field stimulation (EFS) in the trachea, bronchus and bronchiole. 2. EFS applied to the tracheal smooth muscle during contraction induced by 5-HT (10(-5) M) in the presence of atropine (10(-6) M) and guanethidine (10(-6) M) elicited a monophasic NANC relaxation. By contrast, NANC relaxation elicited in the peripheral airway was biphasic, comprising an initial fast followed by a second slow component and L-NAME (10(-5) M) selectively abolished the first component without affecting the second one. In the trachea, L-NAME (10(-5) M) completely suppressed the monophasic NANC relaxation when single or short repetitive stimuli (< 5) with 1 ms pulse duration were applied. However, at higher repetitive stimuli (> 10) with 1 or 4 ms pulse duration, suppression of NANC relaxation was incomplete. 3. In the small bronchi obtained from L-NAME-pretreated cats, EFS applied during contraction induced by 5-HT (10(-5) M) elicited only the slow component of NANC relaxation which is sensitive to tetrodotoxin. 4. In the peripheral airway, a newly synthesized VIP antagonist (10(-6) M) or alpha-chymotrypsin (1 U ml-1) considerably attenuated the amplitude of L-NAME-insensitive relaxation. 5. Single or repetitive EFS consistently evoked excitatory junction potentials (EJPs) in the central and peripheral airways. When tissues were exposed to atropine (10(-6) M) and guanethidine (10(-6) M), single or repetitive EFS did not alter the resting membrane potential. 6. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission and the distribution profile of the two components differs in the central and peripheral airway of the cat.
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PMID:Regional difference in the distribution of L-NAME-sensitive and -insensitive NANC relaxations in cat airway. 857 60

In anaesthetized guinea pigs, adenosine enhances the histamine-induced bronchospasm by means of a mechanism partly involving non-adrenergic-non-cholinergic (NANC) nerves, not related to capsaicin-sensitive neurons (Breschi et al., 1994). In the present paper, we excluded any interference by adenosine with the mediators known to be present in the airway inhibitory NANC system, VIP (vasoactive intestinal polypeptide) and NO (nitric oxide). The use of alpha-chymotrypsin or L-N(G)-nitro-arginine methyl ester (L-NAME) failed to modify the potentiation under study. The effects of adenosine were further investigated by studying whether an increased release of excitatory mediators from non-neural cells, in particular 5-HT (5-hydroxytryptamine, serotonin) and arachidonic products, was involved. In this connection, methysergide did not significantly affect the modulatory action of adenosine, revealing that the release of 5-HT was also not involved. Inhibition was obtained with hydrocortisone and with nordihydroguaiaretic acid, but not with indomethacin or with the mastocyte membrane stabilizer, sodium cromoglycate. This evidence suggests that lipooxygenase products, not derived from mastocytes, probably participate in the potentiating effect of adenosine.
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PMID:Histaminic bronchospasm potentiated by adenosine: investigation of the mechanisms. 927 81

1 Differences in the mechanism of non-adrenergic, non-cholinergic (NANC) inhibitory responses to preganglionic- and post-ganglionic nerve stimulation were investigated in the guinea-pig isolated trachea. 2 Stimulation of the vagus nerve at frequencies above 4 Hz elicited NANC relaxation of the trachealis muscle. Responses to low frequencies of stimulation (4-8 Hz) were abolished by the nitric oxide (NO) synthase inhibitor L-NOARG (10 microM), while a L-NOARG resistant component was observed at higher stimulus frequencies. The L-NOARG-resistant component of NANC inhibitory responses to higher frequencies of vagus nerve stimulation were significantly attenuated by the proteinase alpha-chymotrypsin (2 U/ml), suggesting that a neuropeptide such as VIP may contribute to NANC responses. 3 When postganglionic nerves were stimulated by electrical field stimulation (EFS), responses were readily elicited at frequencies below 4 Hz. Like responses to vagus nerve stimulation, responses to low frequency (<4 Hz) EFS were abolished by L-NOARG while a L-NOARG-resistant component was apparent at higher stimulus frequencies. 4 The L-NOARG-resistant component of NANC inhibitory responses to EFS was sensitive to alpha-chymotrypsin only if stimuli were delivered in either long trains at a low frequency (4 Hz for 10-30 s) or short trains of high frequency (16 Hz for 2.5-7.5 s). 5 Responses to preganglionic nerve stimulation were approximately 35% of the amplitude of responses to EFS in the same preparations. 6 In conclusion, responses to preganglionic and postganglionic NANC inhibitory nerve stimulation in the guinea-pig trachea differ in maximum amplitude, frequency-response characteristics and the contributions of cotransmitters. We suggest that these differences may be explained by filtering of preganglionic input to postganglionic NANC neurons. These results have implications in all studies where EFS is considered to be representative of physiological stimulation of post-ganglionic nerve stimulation.
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PMID:Characterization of non-adrenergic, non-cholinergic inhibitory responses of the isolated guinea-pig trachea: differences between pre- and post-ganglionic nerve stimulation. 1051 Apr 58


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