Desensitization of guinea-pig taenia caeci smooth muscle induced by a low concentration of carbachol.

1. In guinea-pig taenia caeci smooth muscle we have found that 10(-4) mol/L carbachol-induced desensitization to muscarinic agonists develops within 15-30 s, followed by transient resensitization at 1 min, whereas the desensitization to depolarizing high K(+) develops with maximal desensitization at 1 min followed by sustained resensitization up to 30 min. In both cases, Ca(2+)-dependent processes play a crucial role in determining the development of desensitization. 2. To elucidate whether these peculiar processes of desensitization/resensitization may be induced by a lower concentration of carbachol, we examined the development of desensitization induced by 10(-6) mol/L carbachol, because at this concentration carbachol is known to induce biphasic changes in intracellular Ca(2+) concentrations, with a smaller transient increase followed by a larger sustained increase than seen with 10(-4) mol/L carbachol. 3. Contractile responses to muscarinic agonists (carbachol or AHR-602) and high K(+) were desensitized by pretreatment with 10(-6) mol/L carbachol for 30 min in a manner dependent on the presence of extracellular Ca(2+). 4. The development of 10(-6) mol/L carbachol-induced desensitization to these muscarinic agonists in the presence of extracellular Ca(2+) showed three successive phases: fast desensitization within 30 s, followed by transient resensitization at 1 min and the subsequent development of desensitization up to 30 min. In contrast, desensitization to high K(+) did not develop up to 10 min and significant desensitization occurred at 30 min, with no apparent resensitization phase. 5. These results suggest that the characteristics of the Ca(2+)-dependent development of desensitization to muscarinic agonists, but not to high K(+), are well maintained in desensitization induced by a lower concentration of carbachol.