AJEBAK 56 (Pt. 4) 385-394 (1978)
THE EFFECT OF CYCLOHEXIMIDE ON ClIOLECYSTOKININ-EVOKED PANCREATIC JUICE OF THE ANAESTHETIZED RAT by W. A. SEWELL Axn J. A. YOUNG (From the Department of Pliysiology, University of Sydney, N.S.W. 2006, Australia.) (Accepted for publication April 10,1978.) Summar>. Cholecystokinin (CCK) is a major stimulant for enzyme secretion by pancreatic acinar cells. In most animals this enzyme setretion is accompanied by a small volume of chloride-rich "carrier" fluid in which the enzymes are dissolved. In order to determine whether this carrier fluid is secreted independently of the pancreatic digestive enz\nie.s, and how its eomposition is altered by interaetion with them, we liave studied CCK-evoked juice c:olUK'ted from anaesthetized rats tiefore and after admin is tratlou of cyclolieximide, a powerful inliil>itor of protein synthesis. Following treatment with cycloheximide, fluid secretion continued unchanged for 30-40 min but protein excretion declined without appreciable delay towards zero. .-Vs proteiu content declined, the juice bicarbonate content ro.se from .30 to niore than 60 inniole ! ' ' so that the juice resembled that evoked in the nit by seeretin. It is concluded that secretion of (X,'K-evoked fluid is independent of the secretion of digestive enzymes and that the carrier Hnid is actually alkaline, hke secretin-evoked fluid, and only becomes neutral and chloride-rich by interaction with the acidic contents of zymogen granules.
INTRODUCTION. Most published studies on the mechanisms of secretion of fluid and electrolytes by the exocrine pancreas have concentrated on tlie juice produced in response to .seeretin admini.stration. From such studies it bas now been well established that seeretin produces a copious How of pancreatic j"uice that is low in enzyme content btit rich in bicarbonate; good evidence has emerged to implieate the centroaeinar-duetal cells, iu contradistinction to the acinar cells, in the secretion process. In contrast, the study of the role played by cholecystokinin in determining the volume and electrolj/te composition of the panereatie juiee has been somewhat hampered by the lack of a preparation of this hormone that was uiicoiitaininated with seeretin or otlier active polypeptide.s. Recently, however, a pure natural preparation of the hormone (CCK) and a synthetie
386
W. A. SEWELL AND J. A. YOUNG
octapeptide analogue (OP-CCK) have become readily available and studies on the actions of these eompounds in a number of species have been pviblished. Just as seeretin has distinctly different eifect.s in different species (Sewel! and Young, 1975), so also does cholecystakinin. Thus, in the cat, choleeystokinin does not provoke any flow of juiee at all altboiigli it does niodif}- the composition of secret In-evoked jnice (Brown, Harper and Scratcherd, 1967); in the dog, choleeystokinin induces production of a chloride-rich secretion at a moderate rate, somewhat lower than that cansed by secretin (Del)as and Grossman, 197.3); in the rat, the hormone induces a more vigorous How rcspon-sc than does secretin and the bicarbonate concentration does not increase above the plasma-like value found il) the unstiinnlated juice {Sewell and Yonng, 1975; Perlmutter and Martinez, 1978). In tlie rat. in contrast to other speeie.s so far .studied, seeretin, bnt not cbolecystf)kinin, was found to increase the potassium content of panereatie jnice (Sewell and Young, 1975; Folsch and Creutzfeldt, 1976; Perlmutter and Martinez, 1978). TJiese observations have been interpreted as giving strong support to the contention that secretin and choleeystokinin act on distinctly different secretory pathway.s, probably located in different secretory eells (e.g. Case, 1978). The present experiments were planned to elucidate furtlier the mechanism underlying the production of cholecystokinin-evoked juice by the rat pancreas. We administered cyeloheximide, an inhibitor of protein .syntlie.sis, to rats dnring the course of prolonged, continnous adniinishalion of the s\nthi'tic oetapeptide of cJiolecystokinin and studied the effect of elimination of the synthesis of protein on the flow and composition of the pancreatic jniee. In this way we hoped to assess the (ixtent to whicli flow rate and cleetrolyte composition of choleeystokinin-evoked juice was determined by the simnltaneous secretion of exportai>le protein. A preliminary report of this work has already been presented (Coroneo, Kennerson, Sewell and Young, 1975).
MATERIALS AND METHODS,
Male albino Wistar rats (150-250 g body weight) which had been fasted overnight were anaesthetized with lnactin® {Na+ salt of 5-ethyI( l-inpthyipr
THE EFFECT OF CYCLOHEXIMIDE ON ClIOLECYSTOKININ-EVOKED PANCREATIC JUICE OF THE ANAESTHETIZED RAT by W. A. SEWELL Axn J. A. YOUNG (From the Department of Pliysiology, University of Sydney, N.S.W. 2006, Australia.) (Accepted for publication April 10,1978.) Summar>. Cholecystokinin (CCK) is a major stimulant for enzyme secretion by pancreatic acinar cells. In most animals this enzyme setretion is accompanied by a small volume of chloride-rich "carrier" fluid in which the enzymes are dissolved. In order to determine whether this carrier fluid is secreted independently of the pancreatic digestive enz\nie.s, and how its eomposition is altered by interaetion with them, we liave studied CCK-evoked juice c:olUK'ted from anaesthetized rats tiefore and after admin is tratlou of cyclolieximide, a powerful inliil>itor of protein synthesis. Following treatment with cycloheximide, fluid secretion continued unchanged for 30-40 min but protein excretion declined without appreciable delay towards zero. .-Vs proteiu content declined, the juice bicarbonate content ro.se from .30 to niore than 60 inniole ! ' ' so that the juice resembled that evoked in the nit by seeretin. It is concluded that secretion of (X,'K-evoked fluid is independent of the secretion of digestive enzymes and that the carrier Hnid is actually alkaline, hke secretin-evoked fluid, and only becomes neutral and chloride-rich by interaction with the acidic contents of zymogen granules.
INTRODUCTION. Most published studies on the mechanisms of secretion of fluid and electrolytes by the exocrine pancreas have concentrated on tlie juice produced in response to .seeretin admini.stration. From such studies it bas now been well established that seeretin produces a copious How of pancreatic j"uice that is low in enzyme content btit rich in bicarbonate; good evidence has emerged to implieate the centroaeinar-duetal cells, iu contradistinction to the acinar cells, in the secretion process. In contrast, the study of the role played by cholecystokinin in determining the volume and electrolj/te composition of the panereatie juiee has been somewhat hampered by the lack of a preparation of this hormone that was uiicoiitaininated with seeretin or otlier active polypeptide.s. Recently, however, a pure natural preparation of the hormone (CCK) and a synthetie
386
W. A. SEWELL AND J. A. YOUNG
octapeptide analogue (OP-CCK) have become readily available and studies on the actions of these eompounds in a number of species have been pviblished. Just as seeretin has distinctly different eifect.s in different species (Sewel! and Young, 1975), so also does cholecystakinin. Thus, in the cat, choleeystokinin does not provoke any flow of juiee at all altboiigli it does niodif}- the composition of secret In-evoked jnice (Brown, Harper and Scratcherd, 1967); in the dog, choleeystokinin induces production of a chloride-rich secretion at a moderate rate, somewhat lower than that cansed by secretin (Del)as and Grossman, 197.3); in the rat, the hormone induces a more vigorous How rcspon-sc than does secretin and the bicarbonate concentration does not increase above the plasma-like value found il) the unstiinnlated juice {Sewell and Yonng, 1975; Perlmutter and Martinez, 1978). In tlie rat. in contrast to other speeie.s so far .studied, seeretin, bnt not cbolecystf)kinin, was found to increase the potassium content of panereatie jnice (Sewell and Young, 1975; Folsch and Creutzfeldt, 1976; Perlmutter and Martinez, 1978). TJiese observations have been interpreted as giving strong support to the contention that secretin and choleeystokinin act on distinctly different secretory pathway.s, probably located in different secretory eells (e.g. Case, 1978). The present experiments were planned to elucidate furtlier the mechanism underlying the production of cholecystokinin-evoked juice by the rat pancreas. We administered cyeloheximide, an inhibitor of protein .syntlie.sis, to rats dnring the course of prolonged, continnous adniinishalion of the s\nthi'tic oetapeptide of cJiolecystokinin and studied the effect of elimination of the synthesis of protein on the flow and composition of the pancreatic jniee. In this way we hoped to assess the (ixtent to whicli flow rate and cleetrolyte composition of choleeystokinin-evoked juice was determined by the simnltaneous secretion of exportai>le protein. A preliminary report of this work has already been presented (Coroneo, Kennerson, Sewell and Young, 1975).
MATERIALS AND METHODS,
Male albino Wistar rats (150-250 g body weight) which had been fasted overnight were anaesthetized with lnactin® {Na+ salt of 5-ethyI( l-inpthyipr
![[Pancreatic juice and stress ulcers of the rat (author's transl)].](/assets/img/hold.png)
