Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organophosphates (OPs) cause irreversible inhibition of cholinesterases (ChEs) and profound cholinergic stimulation. There are major differences in the response of the dog and cat pancreas to the in vivo administration of Diazinon (O,O-diethyl O-2-isopropyl-4-methyl-6-pyrimidyl phosphothioate), a butyrylcholinesterase (BuChE) inhibitor. Acute edematous pancreatitis is found in the dog but not in the cat. The present experiments were designed to see what effect OP had in vitro on pancreatic exocrine function of dog, cat, and guinea pig, and whether the effects were consistent with an anti-ChE activity. A water-soluble OP agent, tetraisopropyl pyrophosphoramide (iso-OMPA) at 10(-3) M, which like Diazinon inhibits BuChE, was used. Minced pieces of fresh whole pancreata 3 mm in size were taken from 3 dogs, 4 guinea pigs, and 2 cats. The tissues were placed in flasks containing Eagle's solution and gassed with 100% O2. Cumulative amylase release was measured by Phadebas method up to 3 h. At half-maximal acetylcholine (ACH) concentration (10(-5) M), the canine pancreas pretreated with iso-OMPA (10(-3) M) showed a 42-87% greater release of amylase than tissues receiving ACH alone (p less than 0.001). The same potentiated response to ACH was seen in guinea pig pancreas pretreated with iso-OMPA (p less than 0.001), but iso-OMPA pretreatment did not augment the ACH response in the cat. Atropine pretreatment effectively blocked all ACH responses, and there was no effect seen with iso-OMPA alone. In the dog, iso-OMPA in combination with half-maximal carbachol (10(-6) M), or in combination with half-maximal cholecystokinin (CCK-8) stimulation (10(-9) M), provided no potentiated amylase release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the organophosphate iso-OMPA on amylase release by pancreatic lobules of dog, guinea pig, and cat. 244 88

There are two tissue-fixed cholinesterases in dog pancreas: acetylcholinesterase and butyrylcholinesterase. In the present experiments, an organophosphate that only inhibits butyrylcholinesterase (isopropylpyrophosphoramide, or iso-OMPA) was compared with echothiophate and a nonorganophosphate compound, physostigmine. The latter two agents inhibit both cholinesterases. Fresh canine pancreas from anesthetized dogs was minced into fragments and suspended in Eagle's solution gassed with 100% O2. Amylase release was measured by the Phadebas method. In 2-h dose-response studies, there was a fivefold increase in sensitivity to acetylcholine when fragments were preincubated 1 h with iso-OMPA. There was a 1,000-fold increase in sensitivity when fragments were preincubated for 1 h in echothiophate. Basal amylase release in incubates with echothiophate were also increased. In dose-response studies with CCK-8, iso-OMPA was without effect, but echothiophate treatment resulted in a greater total response to CCK-8. There was a corresponding increase in basal output with echothiophate alone. Physostigmine also potentiates the response to CCK-8. Cumulative responses up to 3 h with half-maximal acetylcholine or half-maximal CCK-8 doses showed enhanced total output in fragments preincubated with echothiophate (p less than 0.05). The enhancement effect was atropine-sensitive to hexamethonium ganglionic blockade. In calcium-free medium, the enhancement with echothiophate was greatly reduced but still present. Inhibitors of both cholinesterases in the pancreas cause a greater total amylase release to sub-maximal doses of acetylcholine and CCK-8 than agents that only inhibit butyrylcholinesterase. Though our data do not provide direct proof, the results could be explained by a greater accumulation of endogenous acetylcholine when both cholinesterases are inhibited.
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PMID:Inhibition of acetyl- and butyrylcholinesterase and amylase release from canine pancreas. 247 12