DESENSITIZATION OF GUINEA‐PIG TAENIA CAECI SMOOTH MUSCLE INDUCED BY A LOW CONCENTRATION OF CARBACHOL (Englisch)

Clinical and Experimental Pharmacology and Physiology

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, Ca2+‐dependent processes play a crucial role in determining the development of desensitization.

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 Ca2+ concentrations, with a smaller transient increase followed by a larger sustained increase than seen with 10−4 mol/L carbachol.

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 Ca2+.

The development of 10−6 mol/L carbachol‐induced desensitization to these muscarinic agonists in the presence of extracellular Ca2+ 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.

These results suggest that the characteristics of the Ca2+‐dependent development of desensitization to muscarinic agonists, but not to high K+, are well maintained in desensitization induced by a lower concentration of carbachol.

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