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Propylbenzilylcholine mustard discriminates between two subtypes of muscarinic cholinoceptors in guinea-pig taenia caecum.

A 10-min treatment of isolated guinea-pig taenia caecum with propylbenzilylcholine mustard (PrBCM; 3 x 10(-7) M) inhibited concentration-response curves of 5 full agonists used. A 50-min treatment with PrBCM produced a further inhibition of their curves. However, a 90-min treatment with PrBCM had no further significant inhibitory effect on their curves. Concentration-response curves of 5 partial agonists were completely inhibited by the 50-min treatment with PrBCM (3 x 10(-7) M). The limiting effect of PrBCM observed on the concentration-response curves of the full agonists was not found on the curves of the partial agonists. These results suggest that there are 2 subtypes of muscarinic cholinoceptors, PrBCM-sensitive and -resistant muscarinic receptors, which are discriminated by PrBCM but not by atropine, pirenzepine or AF-DX 116. The pKA value (a negative logarithm of dissociation constant) of carbachol to PrBCM-sensitive receptors is smaller than that to PrBCM-resistant ones, suggesting that the full agonists may be more sensitive to PrBCM-resistant receptors than to PrBCM-sensitive ones. The partial agonists produced contractions of the taenia caecum predominantly through an activation of PrBCM-sensitive receptors, while the full agonists contracted the taenia caecum through the interaction of two subtypes. The responses to nicotine and to electrical stimulation were inhibited by the 50-min treatment with PrBCM, suggesting that PrBCM-sensitive receptors might play a physiological role.