In this work, we discussed and counter-commented Paul J. Weldon's comments on our recent paper (Zhou et al. Proc Natl Acad Sci USA 117:32493, 2020a), where we reported that BCP/BCPO (beta-caryophyllene/caryophyllene oxide) in fresh horse manure is sufficient to drive manure rolling behavior (HMR) in giant panda and attenuate the cold sensitivity of mice by directly targeting and inhibiting transient receptor potential melastatin 8 (TRPM8), an archetypical cold-activated ion channel of mammals. The main question we arise in this response is: “which is the reasonable target of BCP/BCPO? Parasites or TRPM8?” Based on the knowledge of TRPM8-mediated cooling sensation, interaction between BCP/BCPO and TRPM8, BCP/BCPO concentration in horse manure samples, correlation between HMR frequency and habitat temperature, insecticidal activity of BCP/BCPO and thermal ecology of parasites, we prefer a simple idea that BCP/BCPO-induced TRPM8 antagonism bestows the wild giant pandas with cold tolerance at low-ambient temperatures. Compared with the speculation of insecticidal activity induced by HMR behavior, our study provided a comprehensive mechanism to confirm a physiological target of BCP/BCPO during the highly cold-correlated behavior.

在这项工作中，我们讨论并反驳了Paul J. Weldon对我们最近的论文（Zhou等人，Proc Natl Acad Sci USA 117：32493，2020a）的评论，其中我们报道了BCP / BCPO（β-石竹烯/石竹烯氧化物） ）新鲜马粪中的粪便足以驱动大熊猫粪便滚动行为（HMR），并通过直接靶向和抑制瞬态受体电位褪黑素8（TRPM8）（哺乳动物的典型冷激活离子通道）来减弱小鼠的寒冷敏感性。我们在此回应中出现的主要问题是：“ BCP / BCPO的合理目标是什么？寄生虫还是TRPM8？” 基于TRPM8介导的凉爽感觉，BCP / BCPO与TRPM8之间的相互作用，马粪样品中BCP / BCPO浓度，HMR频率与栖息地温度之间的相关性等知识，BCP / BCPO的杀虫活性和寄生虫的热生态学，我们更喜欢一个简单的想法，即BCP / BCPO诱导的TRPM8拮抗作用使野生大熊猫在低温下具有耐寒性。与推测由HMR行为引起的杀虫活性相比，我们的研究提供了一种全面的机制，以确认BCP / BCPO在高度冷相关行为期间的生理目标。