222 Theories of Secretion 



gland to these substances increases progressively with increasing 

 rate of nerve stimulation. The behaviour of all these ten sub- 

 stances could be explained quite satisfactorily on the assumption 

 that there were two pathways by which non-electrolytes could enter 

 the saliva. One of these was a lipoid membrane whose properties 

 were not altered by nerve stimulation. The other was a porous 

 structure the size of whose pores was severely restrictive on the pas- 

 sage of molecules with a diameter greater than about 6-4A. These 

 pores appeared to increase in number or diameter with increasing 

 rate of nerve stimulation, thus leading to an increased permeability. 

 It is of particular interest that the concentration of these substances 

 in the gland substance was not different from that present in the 

 plasma ; difficulty of penetration into the gland cells was not there- 

 fore the cause of the lower concentration of these substances in the 

 saliva as compared with that in the plasma. Further analysis of 

 the mechanism of transfer of the non-electrolytes has been under- 

 taken with urea (Burgen and Seeman, 1958). The submaxillary 

 gland of the dog was isolated from the rest of the animal so that 

 it could be autoperfused with blood ; the venous effluent from the 

 gland was not returned to the animal. The gland was then equili- 

 brated with C 14 -urea by intra-arterial injection and subsequently 

 perfused with non-radioactive blood. In Fig. 10.14 such an experi- 

 ment is shown. Initially, radioactivity was being lost with a half 

 time of 8 minutes. On stimulating the nerve, the output of radio- 

 active urea in the venous blood increased and radioactive urea also 

 appeared in the saliva. However, the specific activity of urea in the 

 saliva was always considerably lower than that in the gland. This 

 could be due to equilibration of radioactive urea secreted by the 

 acinar with non-radioactive urea from the blood during the pas- 

 sage of saliva along the ducts, or to the addition of non-radioactive 

 urea from the blood during the passage of saliva along the ducts. 

 Mathematical analysis of this system can be carried out very satis- 

 factorily and showed that both these processes occurred. On the 

 average, only about one-third of the urea in the saliva was derived 

 from urea secreted by the acini and two-thirds was contributed by 

 diffusion from the blood into the saliva occurring across the ducts. 

 It would, of course, be expected that if non-radioactive urea enters 

 the saliva through the ducts, then also radioactive urea will be lost 

 from the saliva into the blood through the same route. The amount 

 lost was calculated by Burgen and Seeman and compared with the 



