Benzodiazepines and GABA-GABAA receptor system in the cat carotid body.
Benzodiazepines (BZs) suppress ventilation possibly by augmenting the GABA(A) receptor activity in the respiratory control system, but precise sites of action are not well understood. The goals of this study were: (1) to identify GABA(A) receptor subunits in the carotid body (CB) and petrosal ganglion (PG); (2) to test if BZs exert their effects through the GABA(A) receptor in the CB chemosensory unit. Tissues were taken from euthanized adult cats. RNA was extracted from the brain, and cDNA sequences of several GABA(A) receptor subunits were determined. Subsequent RT-PCR analysis demonstrated the gene expression of alpha2, alpha3, beta3, and gamma2 subunits in the CB and the PG. Immunoreactivity for GABA and for GABA(A) receptor beta3 and gamma2 subunits was detected in chemosensory glomus cells (GCs) in the CB and neurons in the PG. The functional aspects of the GABA-GABA(A) receptor system in the CB was studied by measuring CB neural output using in vitro perfusion setup. Two BZs, midazolam and diazepam, decreased the CB neural response to hypoxia. With continuous application of bicuculline, a GABA(A) receptor antagonist, the effects of BZs were abolished. In conclusion, the GABA-GABA(A) receptor system is functioning in the CB chemosensory system. BZs inhibit CB neural response to hypoxia by enhancing GABA(A) receptor activity.
Igarashi
A
A
Division of Physiology Department of Environmental Health Sciences, The Johns Hopkins University, Baltimore, MD, USA. igarashi-ayu@umin.ac.jp
Zadzilka
N
N
Shirahata
M
M
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002344:Carotid Body / Q000187:drug effects* / Q000378:metabolism*; D002346:Carotid Sinus / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D002415:Cats; D000860:Hypoxia / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid