Carbachol differs from classical muscarinic agonists in producing long-term desensitization in smooth muscle.

In the rat and guinea-pig antrum and in the guinea-pig trachea, carbachol (10(-3) M) desensitized the smooth muscle to the contracting action of other muscarinic drugs and BaCl2. In spite of extensive washing, the smooth muscle was completely unresponsive 30 min after the exposure to carbachol and still partially unresponsive after 75 min. None of the classical muscarinic agonists, i.e., acetylcholine, methacholine or bethanechol, showed such a long-term desensitizing effect when tested in identical conditions. Bethanechol (10(-3) M) desensitized the rat antrum heterologously but this desensitization ceased already after 5 min. Carbachol desensitized the rat antral smooth muscle also in a calcium-free incubating medium. It is concluded that the carbachol-induced heterologous long-term desensitization is not related to persisting contraction, changes in receptors or blockade of calcium influx.