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Episodic Spinal 5‐HT7 Receptor Activation Induces Phrenic Motor Facilitation
Author(s) -
Hoffman Michael S.,
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.1232.8
Subject(s) - tropomyosin receptor kinase b , receptor , phrenic nerve , agonist , medicine , endocrinology , chemistry , anesthesia , respiratory system , neurotrophic factors
Spinal activation of Gs protein‐coupled adenosine A2A receptors trans‐activates the high affinity BDNF receptor tyrosine kinase, TrkB, inducing a long‐lasting phrenic motor facilitation (PMF). We hypothesized that other Gs protein‐coupled receptors also elicit PMF. Since serotonin receptors underlie multiple forms of spinal respiratory plasticity, and Gs protein‐coupled 5‐HT7 serotonin receptors are expressed in phrenic motor neurons, we hypothesized that cervical spinal 5‐HT7 receptor activation would induce PMF in anesthetized, vagotomized and ventilated male Sprague Dawley rats. Intrathecal (C4) injections of 5‐HT7 receptor agonist, AS‐19 (4μl, 3×5min; 9μg*kg −1 ), increased phrenic nerve burst amplitude at 60, 90 and 120 minutes post‐injection (44%, 50%, 86±8% baseline, respectively; n=4, p<0.001). Pretreatment with a 5‐HT7 receptor antagonist (SB 269970; 16μg*kg −1 ) prevented AS‐19‐induced PMF (−4%, 0% and 4±9%, respectively; n=3, p<0.05). Thus, spinal 5‐HT7 receptor activation induces a long‐lasting facilitation of phrenic motor output, possibly via TrkB receptor trans‐activation. Although mechanistic details of PMF remain uncertain, molecules that induce respiratory motor facilitation may be useful for treatment of ventilatory control disorders and/or respiratory insufficiency following spinal injury or neurodegenerative disease (NIH HL80209 and HL07654).