Martin P T, Koshland D E
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Proc Natl Acad Sci U S A. 1995 May 23;92(11):5052-6. doi: 10.1073/pnas.92.11.5052.
PC12 cells habituate during repetitive stimulation with acetylcholine, bradykinin, or high potassium. Interspersing these stimulants did not affect the rate of habituation of the others, but it could modulate the amplitude of the norepinephrine secretion each could achieve. Stimulation with acetylcholine inhibited norepinephrine secretion caused by high potassium and bradykinin stimulation, while high potassium had no effect on acetylcholine or bradykinin, and bradykinin increased secretion caused by acetylcholine. Changes in norepinephrine secretion resulting from any of these stimulants correlated with changes in internal calcium levels. Cyclic AMP-, protein kinase C-, and calmodulin-dependent second messenger pathways all modulated norepinephrine secretion caused by acetylcholine and high potassium and showed a distinct hierarchy in their effectiveness. These data demonstrate that different receptor pathways can change the norepinephrine response of one another while not changing the levels of the molecules responsible for habituation.
PC12细胞在用乙酰胆碱、缓激肽或高钾进行重复刺激时会产生习惯化。穿插使用这些刺激物不会影响其他刺激物的习惯化速率,但可以调节每种刺激物所能达到的去甲肾上腺素分泌幅度。乙酰胆碱刺激会抑制高钾和缓激肽刺激引起的去甲肾上腺素分泌,而高钾对乙酰胆碱或缓激肽没有影响,缓激肽会增加乙酰胆碱引起的分泌。这些刺激物中任何一种引起的去甲肾上腺素分泌变化都与细胞内钙水平的变化相关。环磷酸腺苷、蛋白激酶C和钙调蛋白依赖性第二信使途径均调节乙酰胆碱和高钾引起的去甲肾上腺素分泌,且在有效性上呈现出明显的层级关系。这些数据表明,不同的受体途径可以相互改变去甲肾上腺素反应,而不会改变负责习惯化的分子水平。