FUNCTIONAL CHANGES IN STRTC-TUKU 7 1 



microsomes, it appears that the small particles attached to the outer surface of 

 the microsomal membrane are rihonucleoprotein (RNP) particles (30). 



As is generally known, a considerable body of circumstantial evidence suggests 

 that the cytoplasmic RNA is involved in protein synthesis (cf. 5, 3) and points to 

 the microsomes (cf. 3, 21) and to their attached RNP particles (20, 38) as the 

 probable sites of the process. For these reasons, it has already been postulated (27, 

 30, 44) that the voluminous endoplasmic reticulum ot the exocrine cell is con- 

 nected with the large-scale synthesis of proteins which is carried out by this cell, 

 and which results in the production of relatively large quantities of digestive 

 enzymes. After being synthesized, the enzymes are temporarily stored, as assumed 

 by Heidenhain, within the zymogen granules. 



In our study of the exocrine pancreas of the guinea pig, we looked for structural 

 modulations at the level of the endoplasmic reticulum and found that in the 

 starved animal the system is characterized by tight packing, preferred orientation 

 and light content. One hour after feeding, extensive changes appear in a large 

 proportion ( ~40-6o%) of the exocrine cell population. The cavities of the system 

 are distended, the preferred orientation is lost, and relatively large, dense granules 

 are found within the cavities of its distended cisternae (fig. 4). These intracisternal 

 granules are similar in density and fine texture to the zymogen granules of the 

 apical region of the cell, but they are much smaller in size and different in loca- 

 tion (26). To find out what the intracisternal granules contain, we decided to 

 fractionate the pancreas of fed guinea pigs i hour after food intake" and to com- 

 pare the results with those obtained by fractionating the gland of starved animals. 

 In both cases we isolated from the pancreatic breis: /) a heterogeneous nuclear 

 fraction; 2) a zymogen fraction made up primarily of zymogen granules; ^) a 

 mitochondrial fraction; 4) a microsomal fraction which consisted of fragments of 

 the endoplasmic reticulum; and 5) a final supernatant fraction supposedly rep- 

 resenting the cytoplasmic matrix (36). In starved guinea pigs we found that the 

 zymogen fraction accounted for '~^ 40 per cent of the trypsin-activatable pro- 

 teolytic activity of the cell (mainly trypsinogen and chymotrypsinogen) and ~ 

 40 per cent of its ribonuclease activity. In this situation the enzymatic activity 

 of the microsomes was low, but in fed animals it approached both in total 

 amount and in concentration the activity found in the zymogen fraction ( 57). 

 The finding was evidently in agreement with the assumption that the endo- 

 plasmic reticulum is involved in the production of digestive enzymes, and 

 that the intracisternal granules, like the zymogen granules, are temporary de- 

 posits of the enzymes produced. To explore further this possibility, we sub- 

 fractionated the microsomes by differential centrifugation after treating them 

 with low (o.i^f) concentrations of Na deoxycholate. In the case of fed animals, 

 we obtained a heavy subfraction containing intracisternal granules totally or 



- In all experiments the animals were fed after a fast uf 40 to 48 hours. 



