title: Isoflurane inhibits bronchopulmonary C-fiber-mediated apneic response to phenylbiguanide by depressing 5-HT3 receptor function in anesthetized rats.
abstract: A previous study by the authors has shown that isoflurane (ISO), a commonly used volatile anesthetic, has an excitatory effect on bronchopulmonary C-fibers (PCFs). Since selective stimulation of PCFs by action on local 5-HT3 receptors could evoke an apnea, this current study addresses whether inhalation of ISO would facilitate the PCF 5-HT3 receptor-mediated apneic response and, if so, how. In anesthetized and spontaneously breathing rats, inhalation of 5% ISO markedly inhibited the apneic response to intra-atrium injection of phenylbiguanide (PBG, 25 μg/kg), a 5-HT3 receptor agonist, which was contrary to the hypothesis. Extracellular recording of the nodose ganglion neurons in anesthetized, paralyzed and ventilated rats revealed that ISO attenuated the PBG-elicited excitation of pulmonary C neurons. Furthermore, using the patch clamp technique, it was found that ISO depressed the PBG-induced inward current of the pulmonary C neurons labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) instilled previously into the lungs. These results suggest that ISO inhibits PCF 5-HT3 channel functions, and thereby attenuates PCF excitatory response to PBG, likely contributing to the diminution of the PBG-induced apnea by ISO in rats.
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, Albuquerque, NM 87108, United States. Electronic address: zzhang6@salud.unm.edu.
authors.forename: Zhenxiong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhuang
authors.forename: Cancan
authors.initials: C
authors.lastname: Zhang
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001049:Apnea / Q000139:chemically induced / Q000503:physiopathology*; D001645:Biguanides / Q000037:antagonists & inhibitors*; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000294:innervation / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology; D009620:Nodose Ganglion / Q000187:drug effects / Q000502:physiology; D051381:Rats; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology
chemical_list: D001645:Biguanides; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D007530:Isoflurane; C008846:phenyl biguanide
keywords: 5-HT(3) receptor; Breathing; Pulmonary sensory neurons; Volatile anesthetic
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