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THE ORIGIN OF THE ACETYLCHOLINE RELEASED SPONTANEOUSLY FROM THE GUINEA‐PIG ISOLATED ILEUM
Author(s) -
JOHNSON E. S.
Publication year - 1963
Publication title -
british journal of pharmacology and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0366-0826
DOI - 10.1111/j.1476-5381.1963.tb02023.x
Subject(s) - acetylcholine , ileum , guinea pig , new guinea , atropine , chemistry , medicine , biology , pharmacology , endocrinology , history , ethnology
When the guinea‐pig isolated ileum had been previously treated with the anti‐cholinesterase, NN ‐diisopropylphosphodiamidic fluoride (mipafox), and attached to an isotonic lever loaded with 0.5 g, it released acetylcholine into Krebs solution gassed with a mixture of 95% oxygen and 5% carbon dioxide. The amount of acetylcholine spontaneously released depended on the duration of the rest period. Cocaine, procaine or cooling the preparation to 25° C greatly reduced this spontaneous output of acetylcholine, thus providing evidence in support of nervous origin of the ester. Reduction of the calcium ion content of the Krebs solution to one‐twentieth of its usual value or increase in the magnesium ion content four‐fold, changes which inhibit the release of acetylcholine from somatic motor nerve‐endings, inhibited the output of acetylcholine from the ileum. When all the calcium of Krebs solution had been replaced by strontium one‐third of the control output of acetylcholine was obtained, but the smooth muscle of the guinea‐pig ileum would not respond to drugs under these conditions. Strontium could thus partially substitute for calcium in nerves but not in muscle. Hemicholinium‐3 (100 μg/ml.) inhibited the spontaneous release of acetylcholine and 400 μg/ml. of choline was required to reverse the inhibition. It is concluded that cocaine, procaine, cooling, reduction of calcium ion and increase of magnesium ion concentrations all reduce the spontaneous output of acetylcholine, which has its origin in the parasympathetic nerve‐endings of the intramural nerve plexuses. Further, the hemicholinium experiments seem to justify the conclusion that the release of acetylcholine is reduced because synthesis is reduced.