Journal of Applied Physiology AJP: Gastrointestinal and Liver Physiology
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J Appl Physiol (February 15, 2002). doi:10.1152/japplphysiol.00752.2001
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Articles in PresS, published online ahead of print February 15, 2002
J Appl Physiol, 10.1152/jap.00752.2001
Submitted on July 18, 2001
Accepted on February 7, 2002

ACTIVATION OF THE MIDBRAIN PERIAQUEDUCTAL GRAY INDUCES AIRWAY SMOOTH MUSCLE RELAXATION

Musa A Haxhiu1, Bryan K Yamamoto2, Ismail A Dreshaj3, and Donald G Ferguson4*

1 College of Medicine, Department of Physiology and Biophysics, Howard University and Specialized Neuroscience Research Program, Washington, DC, USA; Department of Anatomy, Case Western Reserve University, Cleveland, OH, USA; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA
2 Department of Neuroscience, Case Western Reserve University, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA
3 Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA
4 Department of Anatomy, Case Western Reserve University, Cleveland, OH, USA

* To whom correspondence should be addressed. E-mail: dgf4{at}po.cwru.edu.

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 signaling pathway by: 1) examining the expression of GABAA receptors on airway-related vagal preganglionic neurons (AVPNs) located in the rostral nucleus ambiguus region (rNA), using receptor immunochemistry and confocal microscopy; 2) measuring GABA release within the rNA 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 receptor subtype in this process. We observed that AVPNs located in the rNA region do express the GABAA receptor beta subtype. In addition, we demonstrated that activation of vl PAG induced GABA release within rNA region, and this release was 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 airway smooth muscle tone. These data indicate, for the first time, that activation of vl PAG dilates the airways by a release of GABA and activation of GABAA receptors expressed by AVPNs.




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