192 ELECTROLYTES IN BIOLOGICAL SYSTEMS 



action of specific stimulants such as histamine or carbaminoylcholine or in- 

 hibitors such as thiocyanate or carbonic anhydrase inhibitors, considered in the 

 next section, remains obscure, these agents may develop particularly fruitful 

 lines of investigation. 



COMMENTS CONCERNING THE CARBONIC ACID SYSTEM 



In those isolated instances where it has been possible to identify active trans- 

 port of chloride, for example by the skin of the intact frog or by fish gills, there 

 is an exchange of bicarbonate for chloride. While it is not possible to provide 

 answers to the questions that we may wish to ask, the questions warrant closer 

 attention. Because carbon dioxide is ubiquitous, it is difficult to distinguish 

 between movement of HCO3"", H+ and 0H~. Rather than identify each par- 

 ticular reactant, they will be considered as a group, the carbonic acid system. 



The chloride transport system of the gastric mucosa is linked to the carbonic 

 acid system by its association with H+ secretion and the 'reverse' erythrocyte 

 Hamburger shift in gastric venous blood. 



In the intact animal it is also possible to vary the rate of H+ secretion by 

 hyperventilation, parentral bicarbonate or by bubbling N2 through the secret- 

 ing gastric pouch (2, 61, 63, 64). The dependence of H+ secretion upon CO2 

 can easily be shown in the isolated frog gastric mucosa (46). In figure la, two 

 halves of a stomach, A and B, are alternately exposed to 5% COo for hourly 

 periods with a striking stimulation of H+ secretion. This response is not so 

 much a function of external pH or HCO3" concentration as of the partial pres- 

 sure of carbon dioxide. 



The one investigation that has been responsible more than any other for 

 directing our attention to the carbonic acid system is Davenport's classical 

 demonstration of the uniquely high concentration of carbonic anhydrase within 

 the parietal cell. Its role has been an enigma and until recently it was not even 

 possible to develop evidence in support of its importance. The highly potent 

 carbonic anhydrase inhibitor 'Diamox' (^6063 or 2-acetylamino-i,3,4- 

 thiadiazole-5-sulfonamide) when given parentrally (20-120 mg/kg) causes an 

 85 % inhibition, after a delay of some 30 minutes, in the rate of H+ secretion 

 from the dog Heidenhain pouch (52). A similar depression of H"*" secretion has 

 been noted in the dog mucosal flap with an associated depression of the spon- 

 taneous mucosal potential (88). The reported finding (24) of complete inhibi- 

 tion of acid secretion by isolated frog and toad mucosae when exposed to several 

 other inhibitors in high (17 mM/1.) concentration requires corroboration. 



Several interesting findings emerge from a study of the response of the spon- 

 taneously secreting isolated frog mucosa to Diamox (49). Concentrations of 

 inhibitor i mM/1. or less, whether applied to the serosal or mucosal surface, are 

 without effect, in marked contrast to the sensitivity of the dog stomach in vivo 

 to plasma concentrations which must be less than i mM/1. When the isolated 



