The feeding activity of the nematode Caenorhabditis elegans is regulated by an anatomically well-defined network of 20 enteric neurones that employs small molecule and neuropeptidergic signalling. Two of the most potent excitatory agents are 5-HT and the neuropeptide FLP17A. Here we have examined the role of cAMP in modulating their excitatory actions by pharmacological manipulation of the level of cAMP. Application of the membrane permeable cAMP analogue, dibutyryl-cAMP (1 microM), enhanced the excitatory response to both FLP17A and 5-HT. Furthermore, the adenylyl cyclase activator, forskolin (50 nM), significantly enhanced the excitatory response to both FLP17A and 5-HT. The phosphodiesterase inhibitor, ibudilast (10 microM), enhanced the excitatory response to FLP17A. The protein kinase inhibitor, H-9 dihydrochloride (10 microM) significantly reduced the excitatory response to 5-HT. H-9 dihydrochloride also had a direct effect on pharyngeal activity. The effect of FLP17A and 5-HT on two mutants, egl-8 (loss-of-function phospholipase-Cbeta) and egl-30 (loss-of-function Galphaq) was also investigated. Both these mutants have a lower pharyngeal pumping rate than wild-type which has to be considered when interpreting the effects of these mutations on the excitatory responses to FLP17A and 5HT. However, even taking into consideration the lower basal activity of these mutants, it is clear that the percentage increase in pharyngeal pumping rate induced by FLP17A is greatly reduced in both mutants compared to wild-type. In the case of 5-HT, the effect of the mutant backgrounds on the response was less pronounced. Overall, the data support a role for cAMP in modulating the excitatory action of both FLP17A and 5-HT on C. elegans pharyngeal pumping and furthermore implicate an EGL-30 dependent pathway in the regulation of the response to FLP17A.

中文翻译：

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环 AMP 在调节 5-HT 和兴奋性神经肽 FLP17A 在秀丽隐杆线虫咽肌中的作用的证据。

线虫秀丽隐杆线虫的摄食活动受解剖学上明确定义的 20 个肠道神经元网络的调节，该网络采用小分子和神经肽能信号传导。两种最有效的兴奋剂是 5-HT 和神经肽 FLP17A。在这里，我们研究了 cAMP 在通过 cAMP 水平的药理学操作调节其兴奋作用中的作用。膜渗透营类似物，dibutyryl-营 (1 microM) 的应用增强了对 FLP17A 和 5-HT 的兴奋反应。此外，腺苷酸环化酶激活剂毛喉素 (50 nM) 显着增强了对 FLP17A 和 5-HT 的兴奋反应。磷酸二酯酶抑制剂异丁司特 (10 microM) 增强了对 FLP17A 的兴奋反应。蛋白激酶抑制剂，H-9 二盐酸盐 (10 microM) 显着降低了对 5-HT 的兴奋反应。H-9 二盐酸盐也对咽部活动有直接影响。还调查了 FLP17A 和 5-HT 对两个突变体 egl-8（功能丧失磷脂酶-Cbeta）和 egl-30（功能丧失 Galphaq）的影响。在解释这些突变对 FLP17A 和 5HT 的兴奋反应的影响时，必须考虑这两种突变体的咽泵率低于野生型。然而，即使考虑到这些突变体较低的基础活性，很明显，与野生型相比，FLP17A 诱导的咽泵速率增加的百分比在两个突变体中都大大降低。在 5-HT 的情况下，突变背景对响应的影响不太明显。总体，