Journal of Applied Physiology AJP: Gastrointestinal and Liver Physiology
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J Appl Physiol 93: 440-449, 2002. First published February 15, 2002; doi:10.1152/japplphysiol.00752.2001
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Vol. 93, Issue 2, 440-449, August 2002

Activation of the midbrain periaqueductal gray induces airway smooth muscle relaxation

Musa A. Haxhiu1,2,4, Bryan K. Yamamoto3, Ismail A. Dreshaj4, and Donald G. Ferguson2

1 Department of Physiology and Biophysics, College of Medicine Howard University and Specialized Neuroscience Research Program of Howard University, Washington, DC 20059; Departments of 2 Anatomy, 3 Neuroscience, 4 Pediatrics, and 5 Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

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), by use of receptor immunochemistry and confocal microscopy; 2) measuring GABA release 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 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 the 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.

central control of airway smooth muscle tone; airway dilation; ventrolateral periaqueductal gray; nucleus ambiguus; airway-related vagal preganglionic neurons; parasympathetic nervous system; microdialysis; GABA; GABAA receptors; bicuculline


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