Horio S, Fukui H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi, Japan.
J Pharm Pharmacol. 2001 Feb;53(2):249-54. doi: 10.1211/0022357011775271.
The aim of this study was to investigate the differences between oxotremorine-induced and acetylcholine (ACh)-induced desensitization, particularly under Ca2+-free conditions, in guinea-pig ileal longitudinal muscle, and to elucidate the different mechanisms of desensitization that might exist between these two muscarinic agonists. Pretreatment of the tissue with 10(-7)-10(-5) M oxotremorine (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses to ACh, as did the desensitizing treatment with ACh. However, Ca2+-free conditions significantly reduced oxotremorine-induced desensitization, contrary to the previous findings that Ca2+-free conditions enhanced ACh-induced desensitization. The desensitizing treatment with oxotremorine caused suppression of the responses to high K+ (tonic phase), as did the ACh treatment. Ca2+-free conditions removed this suppression, whereasthis condition enhanced ACh-induced suppression of the K+ response. A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (10(-4) M) had no effect on oxotremorine-induced desensitization of the ACh response. The results suggest that a voltage-gated Ca2+ channel was involved in oxotremorine-induced desensitization, as in ACh-induced desensitization, but that the process of inactivation of Ca2+ channels was different between oxotremorine and ACh, and that oxotremorine-induced desensitization was due not only to Ca2+ channel, but also to other unknown factors. Protein kinase C did not participate in oxotremorine-induced desensitization.
本研究旨在探讨在豚鼠回肠纵肌中，氧化震颤素诱导的脱敏与乙酰胆碱（ACh）诱导的脱敏之间的差异，特别是在无钙条件下的差异，并阐明这两种毒蕈碱激动剂之间可能存在的不同脱敏机制。在正常台氏液中用10⁻⁷ - 10⁻⁵ M氧化震颤素对组织进行预处理（脱敏处理）会导致对ACh反应的脱敏，ACh进行脱敏处理时也是如此。然而，与之前无钙条件增强ACh诱导的脱敏的研究结果相反，无钙条件显著降低了氧化震颤素诱导的脱敏。氧化震颤素的脱敏处理导致对高钾（强直相）反应的抑制，ACh处理也是如此。无钙条件消除了这种抑制，而该条件增强了ACh诱导的对钾反应的抑制。蛋白激酶C抑制剂1-（5-异喹啉磺酰基）-2-甲基哌嗪（10⁻⁴ M）对氧化震颤素诱导的ACh反应脱敏没有影响。结果表明，电压门控钙通道参与了氧化震颤素诱导的脱敏，如同其参与ACh诱导的脱敏一样，但氧化震颤素和ACh之间钙通道的失活过程不同，且氧化震颤素诱导的脱敏不仅归因于钙通道，还归因于其他未知因素。蛋白激酶C不参与氧化震颤素诱导的脱敏。
