Submitted on November 20, 2005
Accepted on August 16, 2006
GABA-A And GABA-B Receptors Differentially Modulate Volume And Frequency In Ventilatory Compensation In Obese Zucker Rats
Ai-Lun Yang1, Ming-Jae Lo2, Hua Ting3, Jwo-Sheng Chen4, Chih-Yang Huang5, and Shin-Da Lee6*
1 Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan
2 Department of Early Childhood Education, National Taichung Teachers College, Taichung
3 Department of Physical Medicine and Rehabilitation, Chung-Shan Medical University Hospital, Taichung
4 Department of Physiology, China Medical University, Taichung
5 Institute of Biochemistry, Chung Shan Medical University, Taichung
6 School of Physical Therapy, China Medical University, Taichung, United States
* To whom correspondence should be addressed. E-mail: shinda_lee{at}yahoo.com.
The aim of this study was to investigate whether GABA-A and/or GABA-B receptor-mediated mechanisms contribute to the impaired ventilatory response and reduced maximal aerobic exercise capacity in obese Zucker rats. Ten lean and ten obese Zucker rats were studied at 12 weeks of age. Ventilation (VE), tidal volume (VT), and breathing frequency (f) during room air breathing and in response to 10 min of hypercapnia(8%CO2) and 30min of hypoxia(10%O2) were measured by the barometric method as well as peak oxygen consumption (VO2peak) was measured by an enclosed metabolic treadmill following the randomized blinded subcutaneous administration of equal volumes of DMSO(vehicle), bicuculline (selective GABA-A receptor antagonist, 1mg/kg), and phaclofen (selective GABA-B receptor antagonist, 1mg/kg). Administration of bicuculline and phaclofen to lean animals had no effect on ventilation and VO2peak. Similarly, phaclofen failed to alter ventilation and VO2peak in obese rats, though it did significantly increase f after 5-20 min of hypoxia. In contrast, bicuculline increased VE and VT relative to DMSO during room air breathing and after 10 to 30 min of hypoxic exposure in obese rats, but it did not increase VE at 5min hypoxemia. Bicuculline increased VO2peak relative to DMSO in obese Zucker rats. We conclude that endogenous GABA acting on GABA-A receptors can modulate ventilation and peak oxygen consumption in obese, but not in lean Zucker rats, whereas endogenous GABA acting on GABA-B receptors modulate the breathing frequency during hypoxia (5-20 min) in obese in a very different manner that it did when acting on GABA-A receptors.
