Sugiya H, Putney J W
Section of Calcium Regulation, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Am J Physiol. 1988 Aug;255(2 Pt 1):C149-54. doi: 10.1152/ajpcell.1988.255.2.C149.
Previous studies have shown that exposure of parotid acinar cells to substance P at 37 degrees C results in activation of phospholipase C, formation of [3H]inositol 1,4,5-trisphosphate (IP3), and persistent desensitization of the substance P response. In cells treated with antimycin in medium containing glucose, ATP was decreased to approximately 20% of control values, IP3 formation was completely inhibited, but desensitization was unaffected. When cells were treated with antimycin in the absence of glucose, cellular ATP was decreased to approximately 5% of control values, and both IP3 formation and desensitization were blocked. A series of substance P-related peptides increased the formation of [3H]IP3 and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, [D-Pro, D-Trp]-substance P, inhibited substance P-induced IP3 formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP3 formation requires agonist activation of a P-type substance P receptor, and that one or more cellular ATP-dependent processes are required for this reaction. However, activation of phospholipase C and the generation of inositol phosphates does not seem to be a prerequisite for desensitization.
先前的研究表明，在37摄氏度下将腮腺腺泡细胞暴露于P物质会导致磷脂酶C激活、[3H]肌醇1,4,5-三磷酸（IP3）形成以及P物质反应的持续脱敏。在用抗霉素处理的含葡萄糖培养基中的细胞中，ATP降至对照值的约20%，IP3形成完全被抑制，但脱敏不受影响。当在无葡萄糖的情况下用抗霉素处理细胞时，细胞ATP降至对照值的约5%，IP3形成和脱敏均被阻断。一系列与P物质相关的肽以相似的效价顺序增加了[3H]IP3的形成并诱导了P物质反应的脱敏。P物质拮抗剂[D-脯氨酸，D-色氨酸]-P物质抑制P物质诱导的IP3形成和脱敏，但不诱导脱敏。这些结果表明，P物质诱导的IP3形成的脱敏需要P型P物质受体的激动剂激活，并且该反应需要一个或多个细胞ATP依赖性过程。然而，磷脂酶C的激活和肌醇磷酸的生成似乎不是脱敏的先决条件。
