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NADPH oxidase activity is necessary for phrenic motor facilitation induced by 5HT2B receptor activation
Author(s) -
MacFarlane Peter M,
Mitchell Gordon S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1232.7
Subject(s) - phrenic nerve , nadph oxidase , facilitation , receptor , agonist , intermittent hypoxia , chemistry , pharmacology , medicine , neuroscience , anesthesia , biology , respiratory system , oxidative stress , obstructive sleep apnea
Acute intermittent hypoxia (AIH) elicits phrenic long‐term facilitation (pLTF), a form of respiratory plasticity that requires activation of spinal 5HT 2 receptors (Mahamed and Mitchell, 2006). AIH‐induced pLTF requires NADPH oxidase‐derived ROS formation (MacFarlane et al ., FASEB J ., 2007). Spinal 5‐HT receptor activation in vivo is sufficient to induce phrenic motor facilitation by an NADPH oxidase‐dependent mechanism, but the specific 5‐HT receptor subtypes involved are not known. In this study, we tested 1) whether spinal 5‐HT 2B receptor activation is sufficient to elicit phrenic motor facilitation (without hypoxia), and 2) whether phrenic motor facilitation following 5‐HT 2B receptor activation requires spinal NADPH oxidase activity. In anesthetized, paralyzed and ventilated rats with constant arterial PO 2 and PCO 2 , episodic intrathecal (i.t.) injections of 5‐HT (1mM) at C 4 (5μl, 3 injections, 5min intervals) or the selective 5‐HT 2B receptor agonist BW723C86 (1mM) both elicited significant phrenic motor facilitation at 60min post‐injections. Pre‐treatment with a single i.t. injection of apocynin (600μM, 12μl, i.t.), an NADPH oxidase inhibitor, blocked phrenic motor facilitation induced by both 5‐HT and BW723C86. Thus, episodic spinal 5‐HT 2B receptor activation is sufficient to elicit phrenic motor facilitation in vivo by a mechanism that requires spinal NADPH oxidase activity. These findings sugest that 5‐HT 2B receptors contribute to serotonin‐dependent phrenic motor facilitation (including AIH‐induced pLTF) by an NADPH oxidase dependent mechanism.