Shuhei Horio and Hideki Moritoki
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences,
University of Tokushima, Shomachi, Tokushima 770, Japan
Abstract: The role of cellular Na+ accumulation in acetylcholine-induced
desensitization was investigated in guinea pig ileal longitudinal muscle.
Desensitization was induced by the pretreatment with acetylcholine (10-4
M, 30 min) and was expressed by the rightward shift in the concentration-response
curve for acetylcholine after the treatment. The same treatment with acetylcholine
caused accumulation of cellular Na+ that amounted to about 3.5-fold of the
control level. To study the relationship between the gain of cellular Na+
and the development of desensitization, we treated the muscle strips with
acetylcholine under the condition in which the external Na+ concentration
ranged from zero to 149.2 mM. The result showed that cellular Na+ content
is closely related to the extent of desensitization; that is, desensitization
was at the lowest level when acetylcholine induced no increase in cellular
Na+, while desensitization developed in proportion to the increase in cellular
Na+ content. However, when cellular Na+ was increased by another method
(by the treatment with ouabain), the inhibition of the acetylcholine response
was far less than that observed in the case of desensitization. We concluded
that both muscarinic stimulation and the accompanying accumulation of cellular
Na+ are required for desensitization to occur in full. This desensitization
could be the result of a muscarinic stimulated and cellular Na+-dependent
mechanism.
Keywords: Ileum (guinea pig), Desensitization, Acetylcholine, Ca2+ channel,
Cellular Na+