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DESENSITIZATION OF GUINEA‐PIG TAENIA CAECI SMOOTH MUSCLE INDUCED BY A LOW CONCENTRATION OF CARBACHOL
Author(s) -
Hishinuma Shigeru,
Sato Ryo,
Saito Masaki
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04704.x
Subject(s) - carbachol , desensitization (medicine) , muscarinic acetylcholine receptor , endocrinology , homologous desensitization , medicine , chemistry , guinea pig , biology , stimulation , receptor
SUMMARY1 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.