Activation of the midbrain periaqueductal gray induces airway smooth muscle relaxation

Musa A. Haxhiu, Bryan K. Yamamoto, Ismail A. Dreshaj, Donald G. Ferguson

Research output: Contribution to journalArticle

18 Scopus citations


In this study, we examined effects of chemical stimulation of the ventrolateral region of the midbrain periaqueductal gray (vl PAG) on airway smooth muscle tone. We observed that in anesthetized, paralyzed, and artificially ventilated ferrets, vl PAG stimulation elicited airway smooth muscle relaxation. To clarify the mechanisms underlying this observation, we examined the GABA-GABAA receptor signalling pathway by 1) examining the expression of GABAA receptors on airway-related vagal preganglionic neurons (AVPNs) located in the rostral nucleus ambiguus region (rNA), by use of receptor immunochemistry and confocal microscopy; 2) measuring GABA release and within the rNA by using microdialysis; and 3) performing physiological experiments to determine the effects of selective blockade of GABAA receptors expressed by AVPNs in the rNA region on vl PAG-induced airway relaxation, thereby defining the role of the GABAA receptors subtype in this process. We observed that AVPNs located in the rNA region do express the GABAA receptor β-subtype. In addition, we demonstrated that activation of vl PAG induced GABA release with the rNA region, and this release associated with airway smooth muscle relaxation. Blockade of the GABAA receptor subtype expressed by AVPNs in the rNA by bicuculline diminished the inhibitory effects of vl PAG stimulation on the airway smooth muscle tone. These data indicate, for the first time, that activation vl PAG dilates the airways by a release of GABA and activation of GABAA receptors expressed by AVPNs.

Original languageEnglish (US)
Pages (from-to)440-449
Number of pages10
JournalJournal of Applied Physiology
Issue number2
StatePublished - Jan 1 2002
Externally publishedYes


  • Airway dilation
  • Airway-related vagal preganglionic neurons
  • Bicuculline
  • Central control of airway smooth muscle tone
  • GABA
  • GABA receptors
  • Microdialysis
  • Nucleus ambiguus
  • Parasympathetic nervous system
  • Ventrolateral periaqueductal gray

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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