Dual opposing actions of STW 5 on TRP receptors mediate neuronal desensitisation in vitro.

Autor: Khalil M; Department of Medicine 1, University Hospital Erlangen, Erlangen, Germany., Zhang Z; Department of Medicine 1, University Hospital Erlangen, Erlangen, Germany., Abdel-Aziz H; Bayer Consumer Health, Darmstadt, Germany., Rabini S; Bayer Consumer Health, Darmstadt, Germany., Ammar RM; Bayer Consumer Health, Darmstadt, Germany; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafr-Elsheikh, Egypt. Electronic address: ramy.ammar@bayer.com., Reeh PW; Institute of Physiology und Pathophysiology, Friedrich-Alexander-Universität Erlangen, Erlangen, Germany., Engel MA; Department of Medicine 1, University Hospital Erlangen, Erlangen, Germany.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2020 Sep 15; Vol. 257, pp. 118112. Date of Electronic Publication: 2020 Jul 17.
DOI: 10.1016/j.lfs.2020.118112
Abstrakt: 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.
Competing Interests: Declaration of competing interest This study was funded by Bayer Consumer Health (Steigerwald Arzneimittelwerk GmbH), Havelstrase 5, 64295, Darmstadt, Germany. HAA, RMA, and SR are fully employed by Bayer Consumer Health. ME and MK received support from the Deutsche Forschungsgemeinschaft (DFG SFB TRR 241/1 TP B05). All other authors report no declarations of interest. The present work was performed in fulfilment of the requirements for obtaining the degree “Dr. med.” for ZZ at the Friedrich-Alexander-University Erlangen-Nürnberg (FAU).
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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