Department of Animal Physiology, Institute of Biology, Leipzig University, Leipzig, Germany.
Carl-Ludwig-Institute for Physiology, Leipzig University, Leipzig, Germany.
Elife. 2020 Sep 30;9:e56738. doi: 10.7554/eLife.56738.
Adhesion-type GPCRs (aGPCRs) participate in a vast range of physiological processes. Their frequent association with mechanosensitive functions suggests that processing of mechanical stimuli may be a common feature of this receptor family. Previously, we reported that the aGPCR CIRL sensitizes sensory responses to gentle touch and sound by amplifying signal transduction in low-threshold mechanoreceptors (Scholz et al., 2017). Here, we show that is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathological conditions. Optogenetic in vivo experiments indicate that CIRL lowers cAMP levels in both mechanosensory submodalities. However, contrasting its role in touch-sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display decreased expression during allodynia. Thus, cAMP-downregulation by CIRL exerts opposing effects on low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action facilitates the separation of mechanosensory signals carrying different physiological information.
黏附型 G 蛋白偶联受体（aGPCRs）参与了广泛的生理过程。它们与机械敏感功能的频繁关联表明，处理机械刺激可能是这个受体家族的一个共同特征。此前，我们报道了 aGPCR CIRL 通过放大低阈值机械感受器中的信号转导，使感觉对轻柔触摸和声音的反应变得敏感（Scholz 等人，2017）。在这里，我们表明在高阈值机械伤害感受器中也表达了，它在生理和病理条件下调节伤害性行为。光遗传学体内实验表明，CIRL 在两种机械感觉亚模式中降低 cAMP 水平。然而，与它在触敏神经元中的作用相反，CIRL 抑制了伤害感受器对机械刺激的反应。与这一发现一致的是，大鼠伤害感受器在痛觉过敏期间显示出 表达减少。因此，CIRL 通过下调 cAMP 对低阈值机械感受器和高阈值伤害感受器产生相反的影响。这种有趣的双极作用有助于分离携带不同生理信息的机械感觉信号。
