Gabapentin Inhibits Catecholamine Release from Adrenal Chromaffin Cells

• Published in: Anesthesiology (Philadelphia) Vol. 116; no. 5; pp. 1013 - 1024
• Main Authors: TODD, Robert D, MCDAVID, Sarah M, BRINDLEY, Rebecca L, JEWELL, Mark L, CURRIE, Kevin P. M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.05.2012
• Subjects: Adrenal Glands - cytology; Adrenal Glands - drug effects; Adrenal Glands - metabolism; Amines - pharmacology; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Calcium - metabolism; Calcium Channels - drug effects; Calcium Signaling - drug effects; Catecholamines - antagonists & inhibitors; Catecholamines - metabolism; Cattle; Cholinergic Agonists - pharmacology; Chromaffin Cells - drug effects; Chromaffin Cells - metabolism; Cyclohexanecarboxylic Acids - pharmacology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - pharmacology; gamma-Aminobutyric Acid - pharmacology; Hemodynamics - physiology; In Vitro Techniques; Medical sciences; Patch-Clamp Techniques; Potassium Chloride - antagonists & inhibitors; Potassium Chloride - pharmacology; Secretory Vesicles - drug effects; Anesthesia; Anticonvulsant; Analgesic; Gabapentin; Chromaffin cell
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0b013e31825153ea

Gabapentin is most commonly prescribed for chronic pain, but acute perioperative effects, including preemptive analgesia and hemodynamic stabilization, have been reported. Adrenal chromaffin cells are a widely used model to investigate neurosecretion, and adrenal catecholamines play important physiologic roles and contribute to the acute stress response. However, the effects of gabapentin on adrenal catecholamine release have never been tested. Primary cultures of bovine adrenal chromaffin cells were treated with gabapentin or vehicle for 18-24 h. The authors quantified catecholamine secretion from dishes of cells using high-performance liquid chromatography and resolved exocytosis of individual secretory vesicles from single cells using carbon fiber amperometry. Voltage-gated calcium channel currents were recorded using patch clamp electrophysiology and intracellular [Ca2+] using fluorescent imaging. Gabapentin produced statistically significant reductions in catecholamine secretion evoked by cholinergic agonists (24 ± 3%, n = 12) or KCl (16 ± 4%, n = 8) (mean ± SEM) but did not inhibit Ca2+ entry or calcium channel currents. Amperometry (n = 51 cells) revealed that gabapentin inhibited the number of vesicles released upon stimulation, with no change in quantal size or kinetics of these unitary events. The authors show Ca2+ entry was not inhibited by gabapentin but was less effective at triggering vesicle fusion. The work also demonstrates that chromaffin cells are a useful model for additional investigation of the cellular mechanism(s) by which gabapentin controls neurosecretion. In addition, it identifies altered adrenal catecholamine release as a potential contributor to some of the beneficial perioperative effects of gabapentin.