THE RESPONSES OF THE GUINEA-PIG ISOLATED INTACT TRACHEA TO TRANSMURAL STIMULATION AND THE RELEASE OF AN ACETYLCHOLINE-LIKE SUBSTANCE UNDER CONDITIONS OF REST AND STIMULATION.

A preparation of the guinea-pig isolated intact trachea is described which allows transmural stimulation of the intrinsic nerves of the tracheal muscle with simultaneous measurement of the volume changes of the trachea caused by contraction or relaxation of the tracheal muscle. The apparatus allows fluid to be removed from the lumen and outside of the trachea for assay of acetylcholine. The response to transmural stimulation over a range of 1 to 50 shocks/sec is first a contraction followed by a relaxation. The contraction is best seen at high frequencies of stimulation and is abolished by atropine. The contraction is enhanced by treatment of the trachea with the anticholinesterase NN-diisopropylphosphodiamidic fluoride (mipafox), and is thus probably due to stimulation of intrinsic cholinergic nerves. The relaxation is maximal at low frequencies of stimulation. After treatment with mipafox a substance resembling acetylcholine is released in the absence of stimulation. The acetylcholine output rises following transmural stimulation, probably due to release of acetylcholine from cholinergic motor nerves. No relationship between frequency of transmural stimulation and release of acetylcholine has been seen in nine of ten experiments. The resting and stimulated release of acetylcholine is not greatly reduced by attempted separation of the tracheal muscle from the bulk of the trachea. This result suggests that acetylcholine outputs from the intact trachea are a measure of release from the smaller tracheal muscle.