Benzodiazepines and GABA-GABAA Receptor System in the Cat Carotid Body

Abstract

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.

Identification of GABA receptors in chick retinal pigment epithelium

“…For example, GABA A receptors have been shown to be located in murine gut [21], in cat carotid body [22], in rat taste bud [23], in human thyroid [24], human hepatocellular [25], human peripheral blood mononuclear cells [26], and human prostate [27]. GABA B receptors have been reported in spider leg mechanosensilla [28], rat testis and sperm [29], the rat olfactory bulb [30], the rat taste bud [23], the rat gastrointestinal tract [31], and rat cardiomyocytes [32].…”

Midazolam in rabbits terminates dysrhythmias caused by intracerebroventricular ropivacaine

“…These results suggest that the effects of midazolam are specific to its ability to potentiate GABA (Asl et al, 2008;Igarashi et al, 2009) and are not the result of generalized CNS depression. We also Values are expressed as mean±SD found that icv midazolam decreased artery blood pressure produced by icv ropivacaine, and that increasing anesthetic depth with isoflurane significantly decreased the artery blood pressure produced by icv ropivacaine in the animals, which indicated that the decrease in artery blood pressure was not simply the result of icv midazolam.…”

Benzodiazepine Oncogenesis as Mediated via Diminished Restorative Sleep Effected Sympathoadrenal Activation

“…In the setting of cocaine abuse, the clinical and magnetic resonance imaging features can be confused with other complications of cocaine abuse and high-risk lifestyles. [2][3][4] …”

“…Since then, one article has raised the possibility of multifocal inflammatory leukoencephalopathy resulting from levamisole-adulterated cocaine, suggesting that this complication can also occur with small amounts of levamisole found in cocaine. 4 We encourage health care professionals to add leukoencephalopathy to the growing list of complications resulting from this adulterant frequently detected in illicit drugs. Though newer benzodiazepine controlled substances are marketed as "nonbenzodiazepines," zolpidem activates identical benzodiazepine sleep modulation ␥-aminobutyric acid type A receptors as classic benzodiazepines, 2 enhancing superficial stage 1/2 sleep interval at the expense of restorative rapid eye movement and stage 3/4 deep slow wave sleep (SWS).…”

“…2,3 Benzodiazepines thereby enhance sleep duration, but at the expense of restorative sleep. Similarly, all benzodiazepines suppress afferent carotid body 4 and medullary ventilatory centers, enhancing central sleep apnea perils. 5 Nocturnally ingested opioids are also well characterized as enhancing sleep duration but suppressing SWS 6 and inducing central sleep apnea, 5 with potential oncogenesis.…”