P2X2/3 and P2X3 receptors contribute to the metaboreceptor component of the exercise pressor reflex

Jennifer L. McCord, Hirotsugu Tsuchimochi, Marc P Kaufman

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The exercise pressor reflex is due to activation of thin fiber afferents within contracting muscle. These afferents are in part stimulated by ATP activation of purinergic 2X (P2X) receptors during contraction. Which of the P2X receptors contribute to the reflex is unknown; however, P2X2/3 and P2X3 receptor subtypes are good candidates because they are located on thin fiber afferents and are involved in sensory neurotransmission. To determine if P2X2/3 and P2X3 receptors evoke the metabolic component of the exercise pressor reflex, we examined the effect of two P2X2/3 and P2X3 antagonists, A-317491 (10 mg/kg) and RO-3 (10 mg/kg), on the pressor response to injections of α,β-methylene ATP (α,β-MeATP; 50 μg/kg), freely perfused static contraction, contraction of the triceps surae muscles while the circulation was occluded, and postcontraction circulatory occlusion in decerebrate cats. We found that the antagonists reduced the pressor response to α,β- MeATP injection (beforeΔ20 ± 3 mmHg; drugΔ11 ± 3 mmHg; P < 0.05), suggesting the antagonists were effective in blocking P2X2/3 and P2X3 receptors. P2X2/3 and P2X3 receptor blockade reduced the pressor response to freely perfused contraction (beforeΔ33 ± 5 mmHg; drugΔ15 ± 5 mmHg; P < 0.05), contraction with the circulation occluded (beforeΔ52 ± 7 mmHg; drugΔ20 ± 4 mmHg; P < 0.05), and during postcontraction circulatory occlusion (beforeΔ15 ± 1 mmHg; drug Δ 5 ± 1 mmHg; P < 0.05). Our findings suggest that P2X2/3 and P2X3 receptors contribute to the metabolic component of the exercise pressor reflex in decerebrate cats.

Original languageEnglish (US)
Pages (from-to)1416-1423
Number of pages8
JournalJournal of Applied Physiology
Volume109
Issue number5
DOIs
StatePublished - Nov 2010
Externally publishedYes

Fingerprint

Purinergic P2X2 Receptors
Purinergic P2X3 Receptors
Reflex
Purinergic Receptors
Cats
Adenosine Triphosphate
Muscles
Injections
Synaptic Transmission
Pharmaceutical Preparations

Keywords

  • A-317491
  • ATP
  • Cats
  • Group III and IV afferents
  • RO-3
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

P2X2/3 and P2X3 receptors contribute to the metaboreceptor component of the exercise pressor reflex. / McCord, Jennifer L.; Tsuchimochi, Hirotsugu; Kaufman, Marc P.

In: Journal of Applied Physiology, Vol. 109, No. 5, 11.2010, p. 1416-1423.

Research output: Contribution to journalArticle

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abstract = "The exercise pressor reflex is due to activation of thin fiber afferents within contracting muscle. These afferents are in part stimulated by ATP activation of purinergic 2X (P2X) receptors during contraction. Which of the P2X receptors contribute to the reflex is unknown; however, P2X2/3 and P2X3 receptor subtypes are good candidates because they are located on thin fiber afferents and are involved in sensory neurotransmission. To determine if P2X2/3 and P2X3 receptors evoke the metabolic component of the exercise pressor reflex, we examined the effect of two P2X2/3 and P2X3 antagonists, A-317491 (10 mg/kg) and RO-3 (10 mg/kg), on the pressor response to injections of α,β-methylene ATP (α,β-MeATP; 50 μg/kg), freely perfused static contraction, contraction of the triceps surae muscles while the circulation was occluded, and postcontraction circulatory occlusion in decerebrate cats. We found that the antagonists reduced the pressor response to α,β- MeATP injection (beforeΔ20 ± 3 mmHg; drugΔ11 ± 3 mmHg; P < 0.05), suggesting the antagonists were effective in blocking P2X2/3 and P2X3 receptors. P2X2/3 and P2X3 receptor blockade reduced the pressor response to freely perfused contraction (beforeΔ33 ± 5 mmHg; drugΔ15 ± 5 mmHg; P < 0.05), contraction with the circulation occluded (beforeΔ52 ± 7 mmHg; drugΔ20 ± 4 mmHg; P < 0.05), and during postcontraction circulatory occlusion (beforeΔ15 ± 1 mmHg; drug Δ 5 ± 1 mmHg; P < 0.05). Our findings suggest that P2X2/3 and P2X3 receptors contribute to the metabolic component of the exercise pressor reflex in decerebrate cats.",
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