Erlichman J S, Coates E L, Leiter J C
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756.
Respir Physiol. 1994 Sep;98(1):27-41. doi: 10.1016/0034-5687(94)90034-5.
We have studied the effects of carbonic anhydrase inhibition on the hypercapnic ventilatory response of the pulmonate snail, Helix aspersa, in an isolated brain-pneumostome preparation. We found that the cell permeant carbonic anhydrase inhibitor, acetazolamide (ACTZ), increased pneumostomal opening and ventilation during normocapnia (2-3% CO2) and decreased the rate of pneumostomal response to step changes in CO2 (4.5%), but did not change the steady-state ventilatory response to elevated CO2 (4.5%) compared to the inactive ACTZ analogue, N2-substituted 2-acetylamino-1,3,4-thiadiazole (Cl 13850). In contrast, the cell impermeant carbonic anhydrase inhibitor, quartenary ammonium sulfonilamide (QAS), had no effect on the pneumostomal response to CO2 compared to Cl 13850. Using Hansson's histochemical technique to stain for carbonic anhydrase activity, we identified a small number of neurons in the subesophageal ganglia that exhibited carbonic anhydrase activity. Some of these cells were in the region of CO2-sensitivity. In conclusion, carbonic anhydrase inhibition slows the ventilatory response to rapid changes in CO2, but does not affect the intrinsic ability of H. aspersa to respond to CO2. The ventilatory effects of carbonic anhydrase inhibition may be attributed to the intracellular actions of the carbonic anhydrase enzyme.
我们在离体脑-气门制备中研究了碳酸酐酶抑制对肺螺类蜗牛（即散大蜗牛）高碳酸血症通气反应的影响。我们发现，细胞可渗透的碳酸酐酶抑制剂乙酰唑胺（ACTZ）在正常碳酸血症（2%-3%二氧化碳）期间增加了气门开放和通气，并降低了气门对二氧化碳阶跃变化（4.5%）的反应速率，但与无活性的ACTZ类似物N2-取代的2-乙酰氨基-1,3,4-噻二唑（Cl 13850）相比，并未改变对升高的二氧化碳（4.5%）的稳态通气反应。相比之下，细胞不可渗透的碳酸酐酶抑制剂季铵磺酰胺（QAS）与Cl 13850相比，对气门对二氧化碳的反应没有影响。使用汉森组织化学技术对碳酸酐酶活性进行染色，我们在咽下神经节中鉴定出少量表现出碳酸酐酶活性的神经元。其中一些细胞位于二氧化碳敏感区域。总之，碳酸酐酶抑制减缓了对二氧化碳快速变化的通气反应，但不影响散大蜗牛对二氧化碳的内在反应能力。碳酸酐酶抑制的通气效应可能归因于碳酸酐酶的细胞内作用。
