Inhibition of acetyl- and butyrylcholinesterase and amylase release from canine pancreas.
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.
Oguchi
Y
Y
Department of Surgery, University of Minnesota Medical School, Minneapolis.
Dressel
T D
TD
Borner
J W
JW
Miller
J
J
Goodale
R L
RL
D000110:Acetylcholinesterase / Q000378:metabolism*; D000681:Amylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D004285:Dogs; D004456:Echothiophate Iodide / Q000494:pharmacology*; D066298:In Vitro Techniques; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010830:Physostigmine / Q000494:pharmacology*; D013770:Tetraisopropylpyrophosphamide / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D013770:Tetraisopropylpyrophosphamide; D002766:Cholecystokinin; D010830:Physostigmine; D004456:Echothiophate Iodide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases; D000681:Amylases