Transient resensitization interrupting the development of carbachol-induced desensitization in smooth muscle of guinea-pig taenia caeci: Ca2+-dependent termination of resensitization.
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(-4) M 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.
Hishinuma
Shigeru
S
Department of Pharmacodynamics, Meiji Pharmaceutical University, Noshio, Kiyose City, Japan. hishi@my-pharm.ac.jp
Saito
Masaki
M
D000818:Animals; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D043587:Receptor, Muscarinic M3 / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000502:physiology
D043587:Receptor, Muscarinic M3; D043562:Receptors, G-Protein-Coupled; D002217:Carbachol; D002118:Calcium