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)

Developmental changes in the response to ganglionic stimulants, nicotine and dimethylphenylpiperazinium, were investigated in rat isolated duodenum by recording isotonic mechanical activity. The duodenal response to nicotine/dimethylphenylpiperazinium (3 x 10(-7) to 10(-3) M) in neonatal rats was contraction, which was blocked by hexamethonium, tetrodotoxin and hyoscine. The response to nicotine/dimethylphenylpiperazinium (10(-6) to 10(-4) M) in the adult duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but by neither guanethidine nor hyoscine. The transition of the response to nicotine/dimethylphenylpiperazinium from contraction to relaxation occurred at around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was significantly inhibited by preincubation with alpha-chymotrypsin, a proteolytic enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline, a P1 purinoceptor antagonist. Nicotine-induced relaxation was desensitized by alpha, beta-methylene ATP, a stable P2x purinoceptor agonist. These results suggest that the contractile response of isolated duodenum to nicotine is mediated through cholinergic transmission in neonatal rats and the relaxant response is mediated through non-adrenergic, non-cholinergic transmission, which involves both peptidergic and purinergic transmission, in adult rats.
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PMID:Developmental changes in the response of rat isolated duodenum to nicotine. 813 72

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

The neurotransmitters mediating relaxation of lower esophageal sphincter (LES) were studied using circular LES strips from adult pigs in organ baths. LES relaxation by sodium nitroprusside (1 nM-3 microM), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP; 1 nM-1 microM), ATP (10 microM-30 mM), and tricarbonyldichlororuthenum dimer (1 microM-1 mM) was unaffected by tetrodotoxin (1 microM) or l-N(G)-nitroarginine methyl ester (l-NAME; 100 microM). Calcitonin gene-related peptide (CGRP; 1 nM-1 microM) did not affect LES tone. ATP relaxation was blocked by 1 microM apamin and the P2Y(1) antagonist MRS 2179 (N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate; 10 microM). Apamin inhibited PACAP relaxation. VIP and PACAP relaxation was blocked by 10 U/ml alpha-chymotrypsin. L-NAME (-62.52 +/- 13.13%) and 1H-[1,2,4]oxadiazole-[4,3-alpha]quinoxalin-1-one (ODQ; 10 microM, -67.67 +/- 6.80%) similarly inhibited electrical LES relaxation, and apamin blocked non-nitrergic relaxation. Nicotine relaxation (100 microM) was inhibited by L-NAME (-60.37 +/- 10.8%) and ODQ (-41.90 +/- 7.89%), and apamin also blocked non-nitrergic relaxation. Non-nitrergic and apamin-sensitive LES relaxation by electrical stimulation or nicotine was strongly inhibited by MRS 2179, slightly inhibited by alpha-chymotrypsin and the P2X(1,2,3) receptor antagonist NF 279 (8,8 cent-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt; 10 microM), and unaffected by tin protoporphyrin IX (100 microM). Porcine LES relaxation after stimulation of intrinsic inhibitory motor neurons is mediated by two main neuromuscular pathways: nitric oxide through guanylate cyclase signaling and apamin-insensitive mechanisms and by non-nitrergic apamin-sensitive neurotransmission mainly mediated by ATP, ADP, or a related purine acting on P2Y1 receptors and a minor contribution of purinergic P2X1,2,3 receptors and PACAP. Nitrergic and purinergic co-transmitters show parallel effects of similar magnitude without major interplay. Our study shows no role for CGRP and only a minor one for VIP and carbon monoxide in porcine LES relaxation.
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PMID:Pharmacologic characterization of intrinsic mechanisms controlling tone and relaxation of porcine lower esophageal sphincter. 1630 17