A PHARMACOLOGICAL ANALYSIS OF THE MODE OF ACTION OF SEROTONIN (5-HYDROXYTRYPTAMINE) UPON THE GUINEA-PIG ILEUM

摘要

1. The mode of action of serotonin (complex of creatinine + 5-hydroxytryptamine) was studied upon the isolated guinea-pig ileum. The stimulating effect of serotonin on the gut was blocked by atropine and appeared, therefore, to be cholinergic in nature. Tachyphylaxis could be observed with small doses (10 μg./15 ml.) if they were added at intervals of less than 3 minutes. 2. Total, though transitory, tachyphylaxis was observed after repeated additions of 40 μg./15 ml. of serotonin. With higher doses, a quick contraction followed by spontaneous return to the normal tonus (while the drug still was in the bath) was observed. For a certain interval of time thereafter the muscle remained refractory to smaller doses of serotonin, but still reacted to other drugs, including nicotine. Sensitivity to small doses of serotonin progressively reappeared. 3. Moderate paralysing doses (50 to 100 μg.) of nicotine depressed or abolished the responses to serotonin and also depressed the responses to histamine, acetylcholine, and bradykinin. If much higher doses (200 to 800 μg.) of nicotine were added, the muscle " escaped " from inhibition by nicotine, responding again to serotonin and increasing in sensitivity to the other drugs, although continuing to be irresponsive to nicotine itself. 4. Decamethonium and hexamethonium had no inhibitory effect upon serotonin action. In some experiments, hexamethonium even potentiated serotonin action. d-Tubocurarine in concentrations that had no effect upon histamine depressed the effects produced by serotonin or nicotine. 5. The action of serotonin was completely blocked by cocaine in doses (10 to 100 μg.) that did not affect histamine or acetylcholine. 5. From these observations the provisional conclusion is drawn that serotonin acts upon the post-ganglionic cholinergic fibres of the intramural nervous system of the guinea-pig ileum.