B-Type Natriuretic Peptide-Induced Delayed Modulation of TRPV1 and P2X3 Receptors of Mouse Trigeminal Sensory Neurons

Abstract

Important pain transducers of noxious stimuli are small- and medium-diameter sensory neurons that express transient receptor vanilloid-1 (TRPV1) channels and/or adenosine triphosphate (ATP)-gated P2X3 receptors whose activity is upregulated by endogenous neuropeptides in acute and chronic pain models. Little is known about the role of endogenous modulators in restraining the expression and function of TRPV1 and P2X3 receptors. In dorsal root ganglia, evidence supports the involvement of the natriuretic peptide system in the modulation of nociceptive transmission especially via the B-type natriuretic peptide (BNP) that activates the natriuretic peptide receptor-A (NPR-A) to downregulate sensory neuron excitability. Since the role of BNP in trigeminal ganglia (TG) is unclear, we investigated the expression of BNP in mouse TG in situ or in primary cultures and its effect on P2X3 and TRPV1 receptors of patch-clamped cultured neurons. Against scant expression of BNP, almost all neurons expressed NPR-A at membrane level. While BNP rapidly increased cGMP production and Akt kinase phosphorylation, there was no early change in passive neuronal properties or responses to capsaicin, α,β-meATP or GABA. Nonetheless, 24 h application of BNP depressed TRPV1 mediated currents (an effect blocked by the NPR-A antagonist anantin) without changing responses to α,β-meATP or GABA. Anantin alone decreased basal cGMP production and enhanced control α,β-meATP-evoked responses, implying constitutive regulation of P2X3 receptors by ambient BNP. These data suggest a slow modulatory action by BNP on TRPV1 and P2X3 receptors outlining the role of this peptide as a negative regulator of trigeminal sensory neuron excitability to nociceptive stimuli.

Capsaicin alleviates abnormal intestinal motility through regulation of enteric motor neurons and MLCK activity: Relevance to intestinal motility disorders

“…Capsaicin receptor known as vanilloid receptors are nonselective cation channel. When activated, they produce depolarization through the influx of Na + , but high Ca 2+ permeability is also important for mediating their response to biological activities . According to the present data, we assumed that competition for regulation of Ca 2+ influx is the predominant mechanism of capsaicin‐induced dual effect.…”

B-Type Natriuretic Peptide is Neither Itch-Specific Nor Functions Upstream of the GRP-GRPR Signaling Pathway

“…However, BNP and NPRA in DRG neurons have been suggested to be a novel auto-feedback nociceptive pathway to modulate inflammatory pain [26] and BNP is a negative regulator of neuronal excitability in response to nociceptive stimuli [27]. Moreover, i.t.…”

Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

“…In addition, substance P (encoded by Tac1 gene) has been identified as the transmitter used by Grpr + neurons in the activation of the last step in the spinal cord itch circuit and the stimulation of spinothalamic projection interneurons (Sakai et al, ). There are several studies on BNP in induction of the delayed modulation of TRPV1 channels and P2X3 receptors in mouse TGNs (Marchenkova, van den Maagdenberg, & Nistri, ; Marchenkova, Vilotti, Fabbretti, & Nistri, ; Marchenkova, Vilotti, Ntamati, van den Maagdenberg, & Nistri, ; Vilotti, Marchenkova, Ntamati, & Nistri, ). But these studies lack further linkage of this function with the involvement of BNP in diseases.…”