NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons
Andrew J. King, Lin Chang, Qian Li, Liansheng Liu, Yaohui Zhu, Pankaj J. Pasricha, Ji Wang, Matthew Siegel, Jeremy S. Caldwell, Susan Edelstein, David P. Rosenbaum, Kenji Kozuka
2024American Journal of Physiology-Gastrointestinal and Liver Physiology19 citationsDOIOpen Access PDF
Abstract
A series of nonclinical experiments support the theory that tenapanor inhibits IBS-C-related pain by strengthening the intestinal barrier. Tenapanor treatment reduced visceral motor responses to nonsensitized levels in two rat models of hypersensitivity and reduced responses to capsaicin in sensitized colonic nociceptive dorsal root ganglia neurons. Intestinal permeability experiments in human colon monolayer cultures found that tenapanor attenuates increases in permeability induced by either inflammatory cytokines or fecal supernatants from patients with IBS-C.
Topics & Concepts
TRPV1Sensory systemFunction (biology)Barrier functionMedicineCell biologyNeuroscienceInternal medicineTransient receptor potential channelBiologyReceptorGastrointestinal motility and disorders