title: Gabapentin inhibits catecholamine release from adrenal chromaffin cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2520, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Todd
authors.forename: Sarah M
authors.initials: SM
authors.lastname: McDavid
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Brindley
authors.forename: Mark L
authors.initials: ML
authors.lastname: Jewell
authors.forename: Kevin P M
authors.initials: KP
authors.lastname: Currie
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002417:Cattle; D018679:Cholinergic Agonists / Q000494:pharmacology; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D000077206:Gabapentin; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D022142:Secretory Vesicles / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; D015220:Calcium Channels; D002395:Catecholamines; D018679:Cholinergic Agonists; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D000077206:Gabapentin; D002118:Calcium