γ-Aminobutyric Acid Type B Receptors with Specific Heterodimer Composition and Postsynaptic Actions in Hippocampal Neurons Are Targets of Anticonvulsant Gabapentin Action

2001 ◽  
Vol 59 (1) ◽  
pp. 144-152 ◽  
Author(s):  
Gordon Y. K. Ng ◽  
Sandrine Bertrand ◽  
Richard Sullivan ◽  
Nathalie Ethier ◽  
Jennifer Wang ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Aminobutyric Acid ◽  
Type B ◽  
Acid Type

scholarly journals Dendritic Assembly of Heteromeric γ-Aminobutyric Acid Type B Receptor Subunits in Hippocampal Neurons

2009 ◽  
Vol 284 (19) ◽  
pp. 13077-13085 ◽  
Author(s):  
Omar A. Ramírez ◽  
René L. Vidal ◽  
Judith A. Tello ◽  
Karina J. Vargas ◽  
Stefan Kindler ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Aminobutyric Acid ◽  
Type B ◽  
Acid Type

Synthesis and Pharmacological Evaluation of Novel γ-Aminobutyric Acid Type B (GABAB) Receptor Agonists as Gastroesophageal Reflux Inhibitors

2008 ◽  
Vol 51 (14) ◽  
pp. 4315-4320 ◽  
Author(s):  
Christer Alstermark ◽  
Kosrat Amin ◽  
Sean R. Dinn ◽  
Thomas Elebring ◽  
Ola Fjellström ◽  
...  
Keyword(s):  
Gastroesophageal Reflux ◽  
Gabab Receptor ◽  
Aminobutyric Acid ◽  
Type B ◽  
Receptor Agonists ◽  
Pharmacological Evaluation ◽  
Acid Type

Dexmedetomidine Prevents Excessive γ-Aminobutyric Acid Type A Receptor Function after Anesthesia

2018 ◽  
Vol 129 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Dian-Shi Wang ◽  
Kirusanthy Kaneshwaran ◽  
Gang Lei ◽  
Fariya Mostafa ◽  
Junhui Wang ◽  
...  
Keyword(s):  
Problem Solving ◽  
Adrenergic Receptor ◽  
Hippocampal Neurons ◽  
Type A ◽  
Surface Expression ◽  
Aminobutyric Acid ◽  
Cell Surface Expression ◽  
Receptor Function ◽  
Anesthetic Drugs ◽  
Acid Type

Abstract What We Already Know about This Topic What This Article Tells Us That Is New Background Postoperative delirium is associated with poor long-term outcomes and increased mortality. General anesthetic drugs may contribute to delirium because they increase cell-surface expression and function of α5 subunit-containing γ-aminobutyric acid type A receptors, an effect that persists long after the drugs have been eliminated. Dexmedetomidine, an α2 adrenergic receptor agonist, prevents delirium in patients and reduces cognitive deficits in animals. Thus, it was postulated that dexmedetomidine prevents excessive function of α5 γ-aminobutyric acid type A receptors. Methods Injectable (etomidate) and inhaled (sevoflurane) anesthetic drugs were studied using cultured murine hippocampal neurons, cultured murine and human cortical astrocytes, and ex vivo murine hippocampal slices. γ-Aminobutyric acid type A receptor function and cell-signaling pathways were studied using electrophysiologic and biochemical methods. Memory and problem-solving behaviors were also studied. Results The etomidate-induced sustained increase in α5 γ-aminobutyric acid type A receptor cell-surface expression was reduced by dexmedetomidine (mean ± SD, etomidate: 146.4 ± 51.6% vs. etomidate + dexmedetomidine: 118.4 ± 39.1% of control, n = 8 each). Dexmedetomidine also reduced the persistent increase in tonic inhibitory current in hippocampal neurons (etomidate: 1.44 ± 0.33 pA/pF, n = 10; etomidate + dexmedetomidine: 1.01 ± 0.45 pA/pF, n = 9). Similarly, dexmedetomidine prevented a sevoflurane-induced increase in the tonic current. Dexmedetomidine stimulated astrocytes to release brain-derived neurotrophic factor, which acted as a paracrine factor to reduce excessive α5 γ-aminobutyric acid type A receptor function in neurons. Finally, dexmedetomidine attenuated memory and problem-solving deficits after anesthesia. Conclusions Dexmedetomidine prevented excessive α5 γ-aminobutyric acid type A receptor function after anesthesia. This novel α2 adrenergic receptor- and brain-derived neurotrophic factor-dependent pathway may be targeted to prevent delirium.

Evaluation of Difluoromethyl Ketones as Agonists of the γ-Aminobutyric Acid Type B (GABAB) Receptor

2013 ◽  
Vol 56 (6) ◽  
pp. 2456-2465 ◽  
Author(s):  
Changho Han ◽  
Amy E. Salyer ◽  
Eun Hoo Kim ◽  
Xinyi Jiang ◽  
Rachel E. Jarrard ◽  
...  
Keyword(s):  
Gabab Receptor ◽  
Aminobutyric Acid ◽  
Type B ◽  
Acid Type

Effects of baclofen on the Hering-Breuer inspiratory-inhibitory and deflation reflexes in rats

1998 ◽  
Vol 274 (2) ◽  
pp. R462-R469 ◽  
Author(s):  
Erin Seifert ◽  
Teresa Trippenbach
Keyword(s):  
Aminobutyric Acid ◽  
Type B ◽  
Rapid Adaptation ◽  
Inspiratory Time ◽  
Airway Occlusion ◽  
Acid Type ◽  
Tracheal Pressure ◽  
The Difference ◽  
Respiratory Phases ◽  
Stimulation Of

The objective of this study was to evaluate effects of baclofen, a γ-aminobutyric acid type B (GABAB) receptor agonist, injected into the nucleus of the solitary tract, on the Hering-Breuer inspiratory-inhibitory (Ti-inhibitory) and deflation reflexes in urethan-anesthetized adult Wistar rats ( n = 7). The Ti-inhibitory reflex was estimated from changes in peak amplitude of the integrated diaphragmatic electromyogram and inspiratory time (Ti) provoked by airway occlusion at end expiration. The deflation reflex was evaluated from changes in Ti and expiration (Te) of the first two breaths (Ti-1, Te-1 and Ti-2, Te-2) immediately after a decrease in tracheal pressure (Ptr). Under control conditions, airway occlusion at end-Te prolonged Ti (66 ± 5%; mean ± SE) and the following Te (54 ± 11%). Decreases in Ptr, from −2 to −5 cmH2O, evoked an increase in Ti and shortening of Te of both breaths. Both effects were Ptr dependent, and Ti-1 and Te-1 differed from Ti-2 and Te-2, suggesting a rapid adaptation to the stimulus. At Ptr of −5 cmH2O, Ti-1 and Ti-2 increased by 30 ± 2 and 43 ± 6%, respectively, and Te-1 and Te-2 decreased by 53 ± 4 and 33 ± 7%, respectively. During unloaded breathing, 60 pmol baclofen prolonged Ti by 120 ± 11% and left Te unaffected. Baclofen abolished vagally mediated changes in Te. On the other hand, the Ti increases caused by either airway occlusion (24 ± 8%) or Ptr of −5 cmH2O (Ti-1; 16 ± 5%) were still significant, but Ti-1 and Ti-2 were not different. A GABAB receptor antagonist, CGP-35348 (2.8 nmol), reversed these effects of baclofen. These results imply that stimulation of GABAB receptors attenuates but does abolish vagally mediated control of Ti. The difference in effects of baclofen on the central and vagal control of Ti and Te suggests different distribution of GABAB receptors in neuronal networks controlling each of these respiratory phases.

Sign in / Sign up

Export Citation Format

Share Document