Ruiz C M, Gomes J C
Department of Pharmacology, Institute of Biosciences, UNESP, Botucatu SP, Brazil.
Alcohol. 2000 Feb;20(2):133-8. doi: 10.1016/s0741-8329(99)00065-8.
We studied the direct effects of ethanol and its metabolites on the guinea pig lung mast cell, and the alterations caused in the histamine release induced by different stimuli. Guinea pig lungs cells dispersed by collagenase were used throughout. High concentrations of ethanol (100 mg/ml), acetaldehyde (0.3-3 mg/ml) and acetic acid (3 mg/ml) induced histamine release that was not inhibited by sodium cyanide (0.3 mM). Lower concentration of ethanol (10 mg/ml) and acetic acid (0.3 mg/ml), but not acetaldehyde, inhibited the histamine release induced by antigen and ionophore A23187. The histamine release induced by phorbol 12-miristate 13-acetate (1 microM) was also inhibited by ethanol (10 mg/ml). Changes in the levels of calcium, glucose and phosphatidic acid did not influence the effect of ethanol. We conclude that high doses of ethanol, acetaldehyde, and acetic acid cause a cytotoxic histamine release by independent mechanisms. Low concentrations of acetic acid inhibit the histamine release by pH reduction. Ethanol acts by a generalized effect that is independent of calcium and glucose suggesting a nonspecific effect that, nevertheless, is not cytotoxic since it can be reversed by washing the cells.
我们研究了乙醇及其代谢产物对豚鼠肺肥大细胞的直接作用,以及不同刺激诱导组胺释放所产生的变化。实验全程使用经胶原酶分散的豚鼠肺细胞。高浓度乙醇(100毫克/毫升)、乙醛(0.3 - 3毫克/毫升)和乙酸(3毫克/毫升)诱导的组胺释放不受氰化钠(0.3毫摩尔)抑制。较低浓度的乙醇(10毫克/毫升)和乙酸(0.3毫克/毫升),但不是乙醛,可抑制抗原和离子载体A23187诱导的组胺释放。佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯(1微摩尔)诱导的组胺释放也受到乙醇(10毫克/毫升)抑制。钙、葡萄糖和磷脂酸水平的变化不影响乙醇的作用。我们得出结论,高剂量的乙醇、乙醛和乙酸通过独立机制导致细胞毒性组胺释放。低浓度乙酸通过降低pH值抑制组胺释放。乙醇通过一种与钙和葡萄糖无关的普遍作用发挥作用,提示一种非特异性作用,不过这种作用不是细胞毒性的,因为通过洗涤细胞可使其逆转。