Gabapentin inhibits catecholamine release from adrenal chromaffin cells.
Gabapentin inhibits catecholamine release from adrenal chromaffin cells.
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DOI：
10.1097/aln.0b013e31825153ea
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发表时间：
2012-05
期刊：
影响因子：
8.8
通讯作者：
Currie KP
中科院分区：
文献类型：
--
作者：
Todd RD;McDavid SM;Brindley RL;Jewell ML;Currie KP
Gabapentin is most commonly prescribed for chronic pain, but acute perioperative effects including preemptive analgesia and hemodynamic stabilization have also been reported. Adrenal chromaffin cells are a widely used model to investigate neurosecretion and adrenal catecholamines play important physiological 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. We 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 (ICa) 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 ICa. 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. We show Ca2+ entry was not inhibited by gabapentin, but was less effective at triggering vesicle fusion. Our work also demonstrates that chromaffin cells are a useful model to further investigate the cellular mechanism(s) by which gabapentin controls neurosecretion. Moreover, it identifies altered adrenal catecholamine release as a potential contributor to some of the beneficial perioperative effects of gabapentin.
