In the previous papers (1-3) it has been reported that some partial agonists accelerate the liberation of acetylcholine from the isolated guinea pig and rat ilea to contract them, yet also antagonize the action of the released acetylcholine and that the intrinsic activity (4) or efficacy (5) of a drug is decided by two factors: acetylcholine liberating activity and inhibitory activity to acetylcholine. In this paper, the receptor mechanisms for partial agonists were studied on the ganglion free taenia caecum from the guinea pig, of which the acetylcholine liberation mechanisms are poor. Some of this work has already been briefly reported (6, 7).
METHODS
AND MATERIALSExperiments were made on strips of the ganglion free taenia caecum (or taenia coli), which were carefully dissected free from the underlying tissues. The strip of the smooth muscle was suspended in a 30 ml organ bath filled with Locke Ringer solution gassed with 95% 02 and 5% CO, and kept at 32°C. Movements of the isolated taenia caecum were recorded on a smoked paper through an isotonic lever to analyse concentration-action curves of test drugs. The effect of dibenamine on the concentration-action curves of the full agonists was cumulatively tested by the method of van Rossum and Ariens (8). When the taenia caecum gave a constant response to butyltrimethylammonium bromide (Bu TMA), concentration-action curves of test drugs were made. After this, the preparation was incubated with dibenamine hydrochloride (10-5 g/ml) for 10 minutes. After washing thoroughly, the concentration-action curves were again obtained with the same test drugs and the preparation was once again incubated with dibenamine hydrochloride (10-5 g/ml) for 10 minutes (the total incubation time was 20 minutes) and a new series of the curves were made with the same test drugs. The above procedure was repeated once more.Another irreversible antagonist of acetylcholine or benzilylcholine mustard was used in the other way which would be described in Results. Locke Ringer solution used contained 9.0 g of NaCI, 0.4 g of KC1, 0.1 g of CaCl2, 0.2 g of MgCI,, 0.2 g of NaHCO3 and 0.5 g of glucose in a litre. In some experiments,