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The Sensitization of The Transient Receptor Potential Vanilloid 1- Mediated Responses By Prostaglandin and Bradykinin
  • sara aldossary,
  • mhammed alsalem,
  • bliar grubb
sara aldossary
King Faisal University
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mhammed alsalem
universit of jordan
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bliar grubb
University of Dundee

Corresponding Author:b.d.grubb@dundee.ac.uk

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Abstract

Transient receptor potential vanilloid type-1 (TRPV1) channels play key roles in chronic pain conditions and are modulated by different inflammatory mediators to elicit heat sensitisation. Bradykinin is a 9-amino acid peptide chain that promotes inflammation. The aim of present study is to investigate how bradykinin and prostaglandin receptors (EP3 and EP4) modulate the sensitisation of TRPV1-mediated responses. Calcium imaging studies of rat dorsal root ganglion (DRG) neurons were employed to investigate the desensitizing responses of TRPV1 ion channels by capsaicin, and the re-sensitization of TRPV1 by bradykinin, then to explore the role EP3 and EP4 receptors in mediating these bradykinin-dependent effects. Immunocytochemistry was used to study the co-expression and distribution of EP4, TRPV1, COX-1 and B2 in rat DRG neurons. Desensitization was seen upon repeated capsaicin application, we show that bradykinin-mediated sensitization of capsaicin-evoked calcium responses in rat DRG neurons occurs is dependent on COX-1 activity, and utilises a pathway that invovles EP4 but not EP3 receptors. The present study provides evidence for a novel signalling pathway through which bradykinin can regulate the TRPV1 ion channel function via the EP4 but not EP3 receptors and provides the anatomical basis for this regulation
03 May 2023Submitted to Basic & Clinical Pharmacology & Toxicology
10 May 2023Submission Checks Completed
10 May 2023Assigned to Editor
10 May 2023Review(s) Completed, Editorial Evaluation Pending
14 May 2023Reviewer(s) Assigned
17 Jul 2023Editorial Decision: Revise Major
23 Oct 20231st Revision Received
25 Oct 2023Review(s) Completed, Editorial Evaluation Pending
25 Oct 2023Submission Checks Completed
25 Oct 2023Assigned to Editor
26 Oct 2023Reviewer(s) Assigned
22 Nov 2023Editorial Decision: Accept