Transient Resensitization Interrupting the Development of Carbachol-induced Desensitization in Smooth Muscle of Guinea-pig Taenia Caed:Ca~(2+)-dependent Termination of Resensitization

摘要

It is important to clarify developmental mechanisms of desensitization because of their great significance in regulation of cellular responsiveness. We have found that carbachol-induced desensitization to carbachol develops in three successive phases in the presence of extracellular Ca~(2+) in the smooth muscle of guinea pig taenia caeci: fast desensitization within 15 s, transient resensitization reaching a peak at 1 min and the subsequent re-development of desensitization to terminate resensitization for up to 30 min. In contrast, in the absence of extracellular Ca~(2+), desensitization develops without resensitization. To further clarify the roles of Ca~(2+) in the formation of the transient resensitization phase, we examined the developmental process of carbachol-induced desensitization in the absence of extracellular Ca~(2+), following the induction of desensitization by a 15-s treatment with carbachol in the presence of extracellular Ca~(2+). Desensitization to carbachol occurred due to pretreatment with 10~4M carbachol for 15 s in normal physiological solution, and continued pretreatment with carbachol in Ca~(2+)-free solution containing 0.2 mM EGTA induced resensitization followed by the obscure progress of re-desensitization for up to 30 min resulting in a long-lasting phase of resensitization. These results suggest that resensitization is promptly terminated by the Ca~(2+)-dependent development of subsequent desensitization for further regulation of cellular responsiveness via G_q protein-coupled Ca~(2+)-mobilizing receptors against sustained stimuli.