The Sensitization of The Transient Receptor Potential Vanilloid 1-
Mediated Responses By Prostaglandin and Bradykinin
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