Dual opposing actions of STW 5 on TRP receptors mediate neuronal desensitisation in vitro
Khalil M, Zhang Z, Abdel-Aziz H, Rabini S, Ammar RM, Reeh P, Engel M (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 257
Article Number: 118112
DOI: 10.1016/j.lfs.2020.118112
Abstract
Aims: STW 5 is an herbal drug combination used for the treatment of functional gastrointestinal disorders (FGIDs) with visceral hypersensitivity as the therapy-resistant hallmark. STW 5 has been clinically proven to alleviate visceral hypersensitivity-related symptoms, including abdominal pain, bloating, nausea, and early satiety. However, the molecular and cellular mechanisms underlying the antinociceptive action of STW 5 remain unknown. Here, we investigate the role of STW 5 in the calcium mobilisation of dorsal root ganglion (DRG) sensory neurons. Main methods: Calcium imaging experiments were performed with freshly dissociated cultured murine DRG neurons isolated from mice by microfluorometry. TRPA1-deficient DRGs, TRPV1-deficient DRGs, TRPA1/V1 double-deficient DRGs, and wild-type DRGs have been used to investigate the role of TRPs ion channels in mediating STW 5 action. Key findings: STW 5 (1.74 and 5.8 mg/ml) induced calcium ion influx into DRG neurons in a concentration-dependent manner. Calcium transients were desensitised during repeated exposure to STW 5, an effect that was facilitated in TRPA1-deficient DRGs and less pronounced in TRPV1-deficient DRGs compared to wild-type (WT) DRGs. Significance: Repeated exposure to STW 5 induced desensitisation of sensory neurons and may ultimately contribute to its proven clinical efficacy against sensory-related symptoms in patients with FGID, including abdominal pain, bloating, nausea, and early satiety. This effect is modulated by the two prominent irritant sensors in nociceptors, TRPA1 and TRPV1.
Authors with CRIS profile
Mohammad Khalil
Lehrstuhl für Physiologie
Zehua Zhang
Medizinische Fakultät
Peter Reeh
Professur für Physiologie
Matthias Engel
Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology
Involved external institutions
Germany (DE)How to cite
APA:
Khalil, M., Zhang, Z., Abdel-Aziz, H., Rabini, S., Ammar, R.M., Reeh, P., & Engel, M. (2020). Dual opposing actions of STW 5 on TRP receptors mediate neuronal desensitisation in vitro. Life Sciences, 257. https://doi.org/10.1016/j.lfs.2020.118112
MLA:
Khalil, Mohammad, et al. "Dual opposing actions of STW 5 on TRP receptors mediate neuronal desensitisation in vitro." Life Sciences 257 (2020).
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