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. 2018 May 18;8:7851. doi: 10.1038/s41598-018-26171-4

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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R568 anti-secretory effects under forskolin-stimulated conditions. Mouse intestines were pretreated with forskolin (FSK, 500 nM, added to the serosal bath), ex vivo, in Ussing chambers to elevate cyclic AMP and excite neurons to induce hypersecretion. Following this pre-treatment, R568 (10 µM) and lidocaine (Lido, 1.6 mM)/TTX (2 µM) were subsequently added to the serosal solution of Ussing chambers with the sequence of their additions indicated. Summarized are steady-state I_sc changes of these pretreated intestines and effects of R568 and lidocaine/TTX. R568 abolishes the forskolin’s excitatory effect in colons of wild-type mice and mice expressing neuronal CaSR (^villinCre/Casr^flox/flox or villin mice) but not in mice lacking neuronal CaSR (^nestinCre/Casr^flox/flox or nestin mice). NS, no significance.