Keely S J, Stack W A, O'Donoghue D P, Baird A W
Department of Pharmacology, University College Dublin, Belfield, Ireland.
Eur J Pharmacol. 1995 Jun 12;279(2-3):203-9. doi: 10.1016/0014-2999(95)00156-f.
Histamine, added to the basolateral side of voltage clamped human colon in vitro, induced a rapid onset, transient inward short circuit current which was concentration dependent over the range 0.01-3 mM. This response was largely due to electrogenic chloride section since it was virtually abolished by bumetanide or by chloride replacement in the bathing solutions. Responses were unaffected by amiloride or acetazolamide. Neither the histamine H2 receptor agonist dimaprit (1 mM) nor the histamine H3 receptor agonist S-(+)-alpha-methyl histamine (1 mM) altered short circuit current. Responses to histamine were significantly reduced by the histamine H1 receptor antagonist mepyramine (1-10 microM) but not altered by the histamine H2 receptor antagonist cimetidine (100 microM) or by the histamine H3 receptor antagonist thioperamide (1 microM). Short circuit current responses to histamine were not altered by tetrodotoxin (1 microM). Piroxicam (10 microM) and nordihydroguaiaretic acid (100 microM) were without effect when used individually but significantly reduced responses to histamine when used simultaneously. These results indicate that histamine stimulates chloride secretion across human colonic epithelium by a mechanism which is mediated exclusively via histamine H1 receptors. This action does not involve intrinsic nerves but appears to be dependent upon eicosanoid synthesis.
在体外对电压钳制的人结肠基底外侧加入组胺，可诱导快速起始的短暂内向短路电流，该电流在0.01 - 3 mM范围内呈浓度依赖性。这种反应主要归因于电生性氯分泌，因为布美他尼或在浴液中置换氯离子几乎可将其消除。反应不受氨氯吡咪或乙酰唑胺的影响。组胺H2受体激动剂二甲双胍（1 mM）和组胺H3受体激动剂S-(+)-α-甲基组胺（1 mM）均未改变短路电流。组胺H1受体拮抗剂美吡拉敏（1 - 10 μM）可显著降低对组胺的反应，但组胺H2受体拮抗剂西咪替丁（100 μM）或组胺H3受体拮抗剂硫代哌酰胺（1 μM）对反应无影响。河豚毒素（1 μM）不改变对组胺的短路电流反应。吡罗昔康（10 μM）和去甲二氢愈创木酸（100 μM）单独使用时无作用，但同时使用时可显著降低对组胺的反应。这些结果表明，组胺通过一种仅由组胺H1受体介导的机制刺激人结肠上皮细胞的氯分泌。这种作用不涉及内在神经，但似乎依赖于类花生酸的合成。
