de Diego Antonio M G, Tapia Laura, Alvarez Rocío M, Mosquera Marta, Cortés Lorena, López Inmaculada, Gutiérrez Luis M, Gandía Luis, García Antonio G
Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
Eur J Pharmacol. 2008 Nov 19;598(1-3):81-6. doi: 10.1016/j.ejphar.2008.09.003. Epub 2008 Sep 16.
Tobacco smokers have an increased risk of cardiovascular disease; this is likely associated to an enhanced catecholamine release by circulating nicotine. Here, we have explored how low concentrations of nicotine in the range of those found in the blood of tobacco smokers, might affect the release of catecholamines in bovine chromaffin cells. We have combined patch-clamp and Ca(2+) imaging techniques to study cell excitability, cytosolic Ca(2+) transients, vesicle movement, and secretory responses. We found that low concentrations of nicotine (1.5-3 microM) did not enhance catecholamine release by themselves. However, they drastically augmented the catecholamine release response triggered by a supramaximal K(+) depolarising pulse. Furthermore, low nicotine concentrations caused slight depolarisation with superimposed action potentials, a transient elevation of Ca(2+) and augmented Ca(2+)-dependent vesicle motion underneath the plasmalemma. We suggest that low nicotine concentrations overload the secretory machinery with secretory vesicles, which cause chromaffin cells to respond with an exaggerated adrenaline release into the circulation during stress. This might contribute to the higher cardiovascular risk of tobacco smokers.
吸烟者患心血管疾病的风险增加；这可能与循环中的尼古丁增强儿茶酚胺释放有关。在此，我们探究了吸烟者血液中所发现浓度范围内的低浓度尼古丁如何影响牛嗜铬细胞中儿茶酚胺的释放。我们结合了膜片钳和Ca(2+)成像技术来研究细胞兴奋性、胞质Ca(2+)瞬变、囊泡运动和分泌反应。我们发现低浓度尼古丁（1.5 - 3 microM）本身并不会增强儿茶酚胺释放。然而，它们会显著增强由超最大K(+)去极化脉冲触发的儿茶酚胺释放反应。此外，低尼古丁浓度会导致轻微去极化并叠加动作电位，使[Ca(2+)]c短暂升高，并增强质膜下Ca(2+)依赖性囊泡运动。我们认为低尼古丁浓度使分泌机制被分泌囊泡过度负载，这导致嗜铬细胞在应激期间向循环中过度释放肾上腺素。这可能是吸烟者心血管风险较高的原因之一。
