Attenuation of autonomic reflexes by A803467 may not be solely caused by blockade of NaV 1.8 channels

Audrey J. Stone, Joyce S. Kim, Katsuya Yamauchi, Victor Ruiz-Velasco, Marc P Kaufman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In decerebrated rats, we determined the dose of A803467, a NaV 1.8 antagonist, needed to attenuate the reflex pressor responses to femoral arterial injections of lactic acid (24 mM; ~0.1 ml) and capsaicin (0.1 μg), agents which stimulate thin fiber afferents having NaV 1.8 channels. We also determined whether the dose of A803467 needed to attenuate these reflex responses affected the responses of muscle spindle afferents to tendon stretch and succinylcholine (200 μg). Spindle afferents are not supplied with NaV 1.8 channels, and consequently their responses to these stimuli should not be influenced by A803467. Pressor responses to lactic acid and capsaicin were not altered by 500. μg of A803467 (n=6). A803467 in a dose of 1. mg, however, significantly reduced (p<0.05; n=12) the pressor responses to lactic acid (23±5 to 7±3δ mmHg) and capsaicin (47±5 to 31±5δ mmHg). Surprisingly, we also found that 1. mg of A803467 reduced the responses of 10 spindle afferents to succinylcholine (34 ± 11 to 4 ± 3δ imp/s; p<0.05) and stretch (83±17 to 0.4±. 1δimp/s; p<0.05). We conclude that A803467 reduces the reflex response to lactic acid and capsaicin; however, it may be working on multiple channels, including NaV 1.8, other NaVs as well as voltage-gated calcium channels.

Original languageEnglish (US)
Pages (from-to)177-182
Number of pages6
JournalNeuroscience Letters
Volume543
DOIs
StatePublished - May 24 2013
Externally publishedYes

Fingerprint

Reflex
Capsaicin
Lactic Acid
Succinylcholine
Muscle Spindles
Calcium Channels
Thigh
Tendons
Injections

Keywords

  • Aδ and C fibers
  • A803467
  • Arterial blood pressure
  • Muscle chemoreflex
  • Muscle spindles
  • Rats

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Attenuation of autonomic reflexes by A803467 may not be solely caused by blockade of NaV 1.8 channels. / Stone, Audrey J.; Kim, Joyce S.; Yamauchi, Katsuya; Ruiz-Velasco, Victor; Kaufman, Marc P.

In: Neuroscience Letters, Vol. 543, 24.05.2013, p. 177-182.

Research output: Contribution to journalArticle

Stone, Audrey J. ; Kim, Joyce S. ; Yamauchi, Katsuya ; Ruiz-Velasco, Victor ; Kaufman, Marc P. / Attenuation of autonomic reflexes by A803467 may not be solely caused by blockade of NaV 1.8 channels. In: Neuroscience Letters. 2013 ; Vol. 543. pp. 177-182.
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abstract = "In decerebrated rats, we determined the dose of A803467, a NaV 1.8 antagonist, needed to attenuate the reflex pressor responses to femoral arterial injections of lactic acid (24 mM; ~0.1 ml) and capsaicin (0.1 μg), agents which stimulate thin fiber afferents having NaV 1.8 channels. We also determined whether the dose of A803467 needed to attenuate these reflex responses affected the responses of muscle spindle afferents to tendon stretch and succinylcholine (200 μg). Spindle afferents are not supplied with NaV 1.8 channels, and consequently their responses to these stimuli should not be influenced by A803467. Pressor responses to lactic acid and capsaicin were not altered by 500. μg of A803467 (n=6). A803467 in a dose of 1. mg, however, significantly reduced (p<0.05; n=12) the pressor responses to lactic acid (23±5 to 7±3δ mmHg) and capsaicin (47±5 to 31±5δ mmHg). Surprisingly, we also found that 1. mg of A803467 reduced the responses of 10 spindle afferents to succinylcholine (34 ± 11 to 4 ± 3δ imp/s; p<0.05) and stretch (83±17 to 0.4±. 1δimp/s; p<0.05). We conclude that A803467 reduces the reflex response to lactic acid and capsaicin; however, it may be working on multiple channels, including NaV 1.8, other NaVs as well as voltage-gated calcium channels.",
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