Abstract
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 language | English (US) |
---|---|
Pages (from-to) | 440-449 |
Number of pages | 10 |
Journal | Journal of Applied Physiology |
Volume | 93 |
Issue number | 2 |
State | Published - 2002 |
Externally published | Yes |
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Keywords
- 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
- Endocrinology
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation
Cite this
Activation of the midbrain periaqueductal gray induces airway smooth muscle relaxation. / Haxhiu, Musa A.; Yamamoto, Bryan; Dreshaj, Ismail A.; Ferguson, Donald G.
In: Journal of Applied Physiology, Vol. 93, No. 2, 2002, p. 440-449.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of the midbrain periaqueductal gray induces airway smooth muscle relaxation
AU - Haxhiu, Musa A.
AU - Yamamoto, Bryan
AU - Dreshaj, Ismail A.
AU - Ferguson, Donald G.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Airway dilation
KW - Airway-related vagal preganglionic neurons
KW - Bicuculline
KW - Central control of airway smooth muscle tone
KW - GABA
KW - GABA receptors
KW - Microdialysis
KW - Nucleus ambiguus
KW - Parasympathetic nervous system
KW - Ventrolateral periaqueductal gray
UR - http://www.scopus.com/inward/record.url?scp=0036021785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036021785&partnerID=8YFLogxK
M3 - Article
C2 - 12133848
AN - SCOPUS:0036021785
VL - 93
SP - 440
EP - 449
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 8750-7587
IS - 2
ER -