significant inhibition occurred. This inhibitory effect of isotonic NaHCO3 at high ph

Transcription

1 J. Physiol. (1981), 314, pp With 5 text- figures Printed in Great Britain TH INTRPLAY BTWN HYDROGN IONS, BICARBONAT IONS AND OSMOLALITY IN TH ANTRIOR DUODNUM MODULATING GASTRIC FUNCTION IN TH CONSCIOUS CALF BY F. R. BLL, M. NOURI AND D.. WBBR From the Department of Medicine, Royal Veterinary College, London NW1 OTU (Received 9 June 198) SUMMARY 1. Gastric emptying, gastric acid and pepsinogen secretion were assessed simultaneously in the conscious calf using the test meal and duodenal perfusion technique (Bell & Mostaghni, 1975). 2. Duodenal infusion of NaCl at a constant osmolality of 3 m-osmole/kg, but with ph ranging from 2- to 12-, did not alter the high level of gastric emptying and secretion already reported for isotonic NaCl or NaHCO3 alone (Bell & Mostaghni, 1975; Bell & Webber, 1979). Gastric function, therefore, is either unaffected by gastric chyme at ph entering the duodenum, or else isotonicity is dominant over ph in activating duodenal receptors which increase motor activity. 3. When the ph of the isotonic NaCl was reduced by the addition of HC1 to below ph 2-, inhibition of gastric function occurred in direct proportion to the amount of titratable acid present in the infusate. The H+ moiety of isotonic duodenal infusates of ph < 2- dominates activation of osmoreceptors and so inhibits motor activity. 4. When the same amount of acid but at differing concentrations and infusion rates was introduced into the duodenum uniform inhibition of gastric function occurred. This result indicates that duodenal acid receptors respond to acid concentration and flow rate to produce an integrated response in proportion to the amount (concentration x volume) of acid present. 5. Isotonic NaHCO3 solutions adjusted to ph by the addition of NaOH, like isotonic NaCl infusions, did not affect gastric function until ph , when significant inhibition occurred. This inhibitory effect of isotonic NaHCO3 at high ph is probably due to C32, since Na2CO3 and Li2CO3, but not LiCl, produce a similar inhibitory effect on gastric function. 6. The inhibitory effect of carbonate gives some support to the existence of a C2-sensor as suggested by Hunt & Knox (1972), whereby increased PCO, produced by intracellular or intercellular neutralization of C32- by duodenal H+ activates acid receptors. But other experiments reported here, where simultaneous perfusion of HC1 and excess NaHCO3 produced a rise in intraluminal Pco,, did not inhibit gastric function, which is contrary to the idea of a direct intraluminal effect of CO2 on duodenal receptors. 7. The ph, P2, PCo2, HCO3 and base excess of venous blood showed no detectable change during duodenal infusion of either acidic or alkaline solutions. Metabolic /81/ $7.5 ) 1981 The Physiological Society

2 332 F. R. BLL, M. NOURI AND D.. WBBR acidosis or alkalosis, therefore, cannot be considered to play any part in controlling gastric function. The results thus corroborate the notion that the receptors controlling gastric function are localized in the intestinal mucosa. 8. Our results suggest that interplay between acid and osmolality of gastric chyme occurs in the rostral part of the duodenum to produce a graded inhibitory effect which by negative feedback modulates the gastric effectors that normally activate smooth muscle, parietal cells and zymogen cells. INTRODUCTION It is recognized that HCl of the gastric chyme modulates gastric functions such as emptying (Hunt & Knox, 1972; Bell & Webber, 1979), secretion (Andersson, Nilsson & Sjodin, 1976; Bell & Webber, 1979) and blood flow (Benyo, Saindor & Szabo, 1979) through duodenal receptors. In man (Hunt & Knox, 1969) and the calf (Bell & Razig, 1973b), as the concentration of HCl in a meal increases so emptying of the stomach decreases. In contrast to the inhibitory effect of duodenal acidification, alkalinization by isotonic NaHCO3 is an effective stimulant of gastric emptying and secretion (Bell & Webber, 1979). The stimulatory effect of certain isotonic solutions is believed to be mediated through duodenal osmoreceptqrs (Hunt & Knox, 1969; Bell & Razig, 1973b). The underlying mechanisms of these correlations are difficult to study using fractional test meals in njan and animals, since the transference of chyme to the duodenum from the stomach during the course of emptying cannot be controlled. Various types of surgical pouches of the stomach have been used to study gastric acid secretion but they cannot be utilized to measure gastric emptying alone or combined with secretion. The duodenal re-entrant preparation in the calf overcomes these difficulties and allows a continual controlled stimulus, with simultaneous collection of gastric effluent without contamination of the duodenal infusate (Bell & Mostaghni, 1975; Bell & Webber, 1979). We have sought to measure the effects on gastric function of discrete amounts of acid and alkali introduced directly into the duodenum. The effect of duodenal infusions using a wide range of ph from has also been examined but, to prevent variability in osmoreceptor stimulation, isotonicity was maintained at a steady state. Since alkali (NaHCO3) is secreted into the lumen of the duodenum in direct proportion to the acid chyme in the duodenum (Lagerl6f, Rudewald & Perman, 196; Meyer, Way & Grossman, 197; Waldum & Burhol, 1979) we have also examined gastric function when mixtures of isotonic NaHCO3 and 6 mm-hcl are perfused simultaneously into the duodenum of the preruminant calf. A brief account of some of our results has been given to The Physiological Society (Bell, Nouri & Webber, 198). MTHODS Animals. Twelve male Friesian calves, 4-5 kg body weight, were used and maintained as described by Bell & Razig (1973a) and Bell & McLeay (1978). Under halothane anaesthesia the duodenum was transacted 5 cm distal to the pylorus and reconnected by re-entrant cannulae (Bell & Mostaghni, 1975). The stomach (abomasum) was fitted with a single large cannula. Calves were prepared when about 2 weeks old; experiments were commenced a week after surgery and continued

3 DUODNAL ACID CONTROLS GASTRIC FUNCTION 333 during the next 5-6 weeks. The preparation permits the instillation of a test meal into the empty stomach and the direct measurement of the gastric effluent collected from the proximal cannula during the course of controlled duodenal infusion through the distal duodenal cannula. xperimental procedure. The experimental protocol was that described by Bell & Mostaghni (1975) except that test meals were always isotonic saline at ph 6&, and contained 7 mg/l. of phenol red. Solutions of NaCl adjusted to ph with sufficient HCI or NaOH, but with a final osmolality of 3 m-osmole/kg, were used for duodenal infusion. Comparison was made with other infusates containing NaHCO3 adjusted with NaOH to ph In addition Na2CO3 (ph 11-2 and 12-), Li2CO3 (ph 11 1) and LiCI (ph 6) solutions were used when necessary. All alkaline solutions were also prepared so as to contain 3 m-osmole/kg. Osmolality was measured with an osmometer (Fiske Instruments, Model 33). The solutions were always infused into the duodenum at 1 ml./min, except where reference to change in rate is mentioned specifically, for 1 min before and 45 min after the instillation of the meal into the stomach. Duodenal infusions were made at room temperature since variation in the temperature of the infusate does not affect gastric function (Webber, Nouri & Bell, 198). Gastric effluent was collected at 5 min intervals and acid and pepsin estimations carried out as described previously (Bell & Webber, 1979). Blood was taken from the jugular vein via an indwelling cannula (Portex /5/4). The blood samples were taken anaerobically into heparinized, siliconized syringes and ph, PcO2, PO2 and HC3- measured with a Corning-L ph/blood gas meter. Results were evaluated statistically using Student's t test for unpaired values, P < 5 being taken as the level of significance. 1 8 cm C ra 6 2) * 12- ph of infusate Fig. 1. mptying of test meals, expressed as the mean percentage (±S..) remaining in the stomach after 45 min. The duodenum was perfused with isotonic NaCl solutions of ph ; adjustment of ph was made with HCI or NaOH. Significant differences compared with the infusate at ph 7 are shown by *** (P < -1). ach value is the mean of five experiments in four or five calves. RSULTS The gastric effect of duodenal infusion of NaCl solutions, ph Over the ph range 2O-12-, 75 % of the test meal was emptied from the stomach, which is the degree of emptying normally associated with isotonic NaCl or NaHCO3 duodenal infusions (Fig. 1). This finding indicates that the response to the infusate

4 334 F. R. BLL, M. NOURI AND D.. WBBR was mediated by osmoreceptors and that the variable ph of the infusate had no discernible effect. When the NaCl infusions were below ph 2- significant decreases in gastric emptying developed, culminating in complete retention of the test meal at ph 12 (Fig. 1). When the results of perfusion of isotonic NaCl solutions ranging from ph 1-2 to 7- are expressed as the amount of titratable acid being delivered to the duodenum a significant correlation with gastric emptying can be demonstrated (Fig. 2A). This A c 7,Fs 6 5 'a B 1 3 r = -927 P<.1 (n = 35) I I II I I LO * _- 5 C 3 r = P<.1 (n = 35i Jul _'., 1 I I ~~~~I C~ LO. CcL._ f r = P<.1 (n = 35) _L- I I I I I I I 1 3 Titratable acid infused into duodenum (m-equiv/55 min) Fig. 2. Gastric emptying (A), acid secretion (B) and pepsin secretion (C) correlated with the amount of titratable acid (concentration x volume x time) infused into the duodenum. Values are mean + S.. Regression lines were calculated by the least squares method; association between the variables is shown by the significant correlation coefficients.

5 DUODNAL ACID CONTROLS GASTRIC FUNCTION 335 result suggests that it is the amount of H+ in the infusate rather than the ph of the infusion which affects duodenal acid receptors. The effect can be compared to a dose-response curve of the effect of H+ as a mediator of inhibition of gastric muscle with maximum response at approximately 35 m-equiv/55 min (Fig. 2A). A similar inhibition of secretion of gastric acid (Fig. 2B) and pepsin (Fig. 2C) also occurred as the amount of titratable acid was increased in the duodenum. 1 r- 8 F ol C :C a) a) 6 V 4 h A B C e o I L I L Duodenal infusate Fig. 3. The effect on gastric emptying ofduodenal infusion ofacid at different concentrations and infusion rates but always producing 11 m-equiv/55 min. A, [H+] = 4 m-equiv/l.; ph 1-4, infusion rate = 5 ml./min. B, [H+] = m-equiv/l.; ph 1-7, infusion rate = 1 ml./min. C, [H+] = 1 m-equiv/1., ph 2-, infusion rate = ml./min. The infusate was always adjusted to 3 m-osmole/kg with NaCl. ach mean+s..m. is from five experiments in three calves. To test the effect of H+ as an inhibitor of gastric emptying infusions were prepared so that equal masses of H+ were introduced into the duodenum in 55 min but at three different infusion rates and concentrations (Fig. 3). The figure of 11 m-equiv/55 min titratable acid was chosen as a mid-point stimulus which could be expected to produce 56 % emptying of a test meal (see Fig. 2 A). The results of the fifteen experiments illustrated in Fig. 3 show a very similar degree of inhibition of emptying, indicating that acid receptors in the duodenum respond to H+ mass rather than to concentration, which is normally measured as ph.

6 336 F. R. BLL, M. NOURI AND D.. WBBR The gastric effect of isotonic duodenal infusions of NaCi and NaHCO3, ph8#)-1 The effect on gastric emptying of duodenal infusion of isotonic NaCl solutions adjusted with NaOH to ph is shown in Fig. 1. The same rapid rate of emptying and increased secretion which occurred shows that high ph and increasing OH- concentration did not affect gastric function. By contrast, when isosmolal A n= c= T 8 C M 6 LO ~1 *. ~ ph of infusate: Na2CO3 Li 2CO3 LiCI Duodenal infusate Fig. 4. The effect on gastric emptying (A) and acid secretion (B) of duodenal infusion with alkaline solutions (n, number of experiments; c, number of calves). Significant inhibition of gastric function (compared with ph 8-1) occurred when NaHCO3 infusates were alkalinized to ph 11 and 12- (* P< 5; ** P< 1; *** P< 1). A similar inhibition with Na2CO3 or Li2CO3 infusion also occurred. NaHCO3 solutions of the same ph range ( ) were infused, significant inhibition of gastric emptying and acid secretion occurred at ph 11 and 12 (Fig. 4). The probable importance of CO32 in causing this effect by isotonic NaHCO3 at these high ph values is corroborated by a similar result when isotonic Na2CO3 or Li2CO3 solutions at high ph were used as duodenal infusates: the same degree of inhibition of emptying and secretion was observed irrespective of the cation present (Fig. 4).

7 DUODNAL ACID CONTROLS GASTRIC FUNCTION 337 This conclusion was supported by the further observation that isotonic LiCl infused at ph 6- (Fig. 4) produced similarly high rates of emptying and secretion to those found with isotonic NaCl. Intraluminal CO2 production on dual infusion of HCl and NaHCO3 The acid of gastric chyme is in large part neutralized by secretion of NaHCO3 from the intestine and pancreas, with an increase in luminal CO2 which might be detected by mucosal receptors. This hypothesis was tested in a limited series of experiments when concurrent infusion of acid (HCl, 1 mm, 5 ml./min) and excess NaHCO3 (143 mm, 5 ml./min) was made by separate but closely adjacent instillation into the duodenal cannula onto the duodenal mucosa. The resultant combined infusate which now bathed the mucosa at the set rate of 1 ml./min had ph 2-5 and an osmolality of 25 m-osmole/kg. This experiment duplicates the infusion of 6 mm-hcl at 1 ml./min of the earlier experiments but mimics complete neutralization of the acid in the intestine by alkaline secretions. In five experiments in two calves gastric emptying was not significantly inhibited, indicating the absence of H+ in the lumen. The amount of test meal remaining in the stomach after 45 min (mean + S..M.) was 4.7 +±4.3 o (cf. Fig. 1). These experiments show that acid in the duodenum is readily neutralized by NaHCO3 to abolish the inhibitory effects on gastric function and also that increased intraluminal PCO, does not have an inhibitory effect. Blood acid-base values following acid or alkaline perfusion of the duodenum Blood samples were collected from the jugular vein before, during and after perfusion of the duodenum with acid or alkali. Duodenal infusion produced no change in ph, Po2, Pco2, HCO3- or base excess in the blood, which shows that neither the inhibitory nor stimulatory effects are mediated through a detectable change in the circulating blood. DISCUSSION The conscious preruminant calf provides a satisfactory preparation for studying mammalian gastric physiology since the abomasum at this stage is the homologue of the stomach of other mammals (Bell, 198). Furthermore, the calf tolerates duodenal cannulation well, which permits easy continuous collection of gastric effluent distinct from duodenal infusions (Bell & Mostaghni, 1975; Blum, Koelz, Schmid, Sauberli, Largiader & Krejs, 1975). The calf also has the anatomical advantage over other experimental mammals and man that the bile duct enters the duodenum cm distal to the pylorus and the functional pancreatic duct a further 15 cm caudally (F. R. Bell & D.. Webber, unpublished results). This is an important factor in duodenal perfusion studies since the proximal duodenum may be the primary site of receptors (Andersson & Uvnas, 1961; Cooke, 1977; Bell & Holbrooke, 1979). Furthermore, the duodenal ph changes quickly from acid to alkaline values in the calf with increasing distance from the pylorus (Mylrea, 1966). In addition, in our present study in the calf we have shown that duodenal infusion of acid or alkali does not affect acid-base parameters of the blood, an important corroboration of the view that receptors controlling gastric function are probably localized in the

8 338 F. R. BLL, M. NOURI AND D.. WBBR intestinal mucosa. It is possible, however, that other visceral receptors, for example those in the portal area, could be affected by local changes in blood parameters not reflected in the systemic circulation. In our experiments the ph per se did not have any effect on gastric function when duodenal infusates were in the range ph This firm evidence corroborates the view that the rate of gastric emptying and secretion is not directly dependent on the ph of the gastric chyme reaching the anterior duodenum (Hunt & Knox, 1962). The small amounts of H+, as indicated by ph > 2-, either do not activate duodenal acid receptors to inhibit gastric function or else inhibitory activation by such receptors is overwhelmed by the stimulatory effect of isotonic solutions on osmoreceptors. In addition the results suggest that isotonic duodenal chyme maintains the continual transfer of gastric effluent to the duodenum and when the duodenal ph > 2- is probably the main stimulus. When the duodenal ph < 2- the position changes, for as the H+ content of the duodenal infusate increases a rectilinear relationship develops between inhibition of gastric function and the amount of titratable acid. The inhibitory effect of acid on gastric emptying has been confirmed many times since it was first demonstrated in dogs by Hirsch (1893). The test meal technique (Hunt & Spurrell, 1951), however, has the disadvantage of variation in gastric secretion and gastric emptying which makes it impossible to predetermine delivery of acid to the duodenum, as was clearly shown in man by Hunt & Knox (1969). In the conscious calf preparation our experiments show clearly that titratable H+ affects acid receptors to modulate the stimulatory effect of osmolality on gastric function (Fig. 2A) and that the inhibition of gastric emptying becomes total when anterior duodenal chyme has the equivalence of O6 m-equiv/min HCl. The mechanism of stimulation of the intestinal acid receptor is a matter of conjecture; Hunt & Knox (1972) suggest that this receptor is excited by duodenal chyme but do not accept the possibility ofa simple situation whereby H+ concentration produces a proportional increase in activation between ph 2- and ph 1-2. Our results are compatible with the possibility that H+ could generate such stimuli directly, as proposed by Konturek & Grossman (1965). Hunt & Knox (1972) suggest that absorbed H+ is titrated locally by HCO3- and that subsequent dehydration of H2CO3 produces CO2 which activates the receptor. In our experiments, where carbonates cause inhibition of gastric function, a similar mechanism could be involved wherein the C32- is neutralized by intracellular or intercellular H+ to yield H2CO3 and CO2. It appears unlikely, even under abnormal circumstances, that values of ph ever occur in the duodenum, although we have shown that even with duodenal infusates of ph 12 the blood ph is unchanged. It has been suggested by Rune (1968) and Robinson & Winship (1969) that a rise in Pco2 in the duodenal lumen may be responsible for the inhibitory effects produced by acidification. The results of our experiments to test this idea by dual perfusion of 1 mm-hcl and NaHCO3 do not support this view, for gastric emptying was not significantly inhibited. This shows that raised PCO2 in the lumen is unimportant and that direct CO2 stimulation of 'acid' receptors in the duodenum does not occur.

9 DUODNAL ACID CONTROLS GASTRIC FUNCTION 339 The interplay of osmoreceptors and H+ receptors in controlling gastric function We have shown clearly that duodenal infusions of isotonic NaCl and NaHCO3 of widely varying ph have identical effects on gastric function. When duodenal chyme is not isotonic, increased acid concentration would raise the osmolality and thus affect both osmoreceptors and acid chemoreceptors. An evaluation of forty-eight experiments performed previously in our laboratory on sixteen calves during duodenal acid infusions without adjustment of osmolality is shown in Fig. 5. Higher rates of gastric a - C a).t 9 1 u o l 1-8 CD * 6 By4 _, 1 3 Titratable acid infused into duodenum (m-equiv/55 min) Fig. 5. Gastric emptying when acid duodenal infusates are maintained at 3 m-osmole/kg compared with results from previous experiments in which osmolality was not controlled. Present experiments, interrupted lines (Fig. 2 A); previous experiments, continuous lines (based on data from Bell & Mostaghni (1975), Bell & Holbrooke (1979), Bell & Webber (1979) and Webber et al. (198): in forty-eight experiments on sixteen calves, r = -867, P < o1). emptying were always associated with isotonic infusates when compared with hypotonic infusates, the difference in gastric emptying rate being greater as the difference in osmolality increased (Fig. 5). At the points where no titratable acid is delivered to the duodenum - that is water, and isotonic saline at ph a difference of o in gastric emptying occurs. This effectiveness of both NaCl and NaHCO3 in eliciting gastric emptying compared with water has been noted previously

10 34 F. R. BLL, M. NOURJ AND D.. WBBR (Hunt, 1956; Hunt & Knox, 1969; Bell & Razig, 1973b). It is also apparent from Fig. 5 that as the concentration of acid rises to 35 m-equiv then osmolality effects are superseded and then suppressed. When isotonic duodenal infusions with the same mass of H+ but varying in acid content and infusion rate were carried out the gastric responses were identical. This result strongly suggests that duodenal acid receptors respond to the amount of acid presented to the duodenum from the stomach by integrating acid concentration and flow rate. Our results further extend the view of Konturek & Grossman (1965) that the degree of acid receptor stimulation generates a graded inhibitory effect to affect all three functions of the stomach in the same direction. This result indicates also that a single type of acid receptor occurs in the proximal duodenum, which by negative feedback modulates the effectors which normally activate gastric muscle, parietal cells and zymogen cells. This work was supported by a grant from the Agricultural Research Council. RFRNCS ANDRSSON, S., NILSSON, G. & SJODIN, L. (1976). The significance of the duodenal bulb for gastric functions in the dog. Can. J. Gastroenterol. 11, supply. 42, ANDRSSON, S. & UVNAS, B. (1961). Inhibition of postprandial gastric secretion in Pavlov pouches by instillation of hydrochloric acid into the duodenal bulb. Gastroenterology 41, BLL, F. R. (198). The mechanisms controlling abomasal emptying and secretion. In Digestice Physiology and Metabolism in Ruminants, ed. RUCKBUSCH, Y. & THIVND, P., pp Lancaster: MTP Press. BLL, F. R. & HOLBROOK, S.. (1979). The sites in the duodenum of receptor areas which affect abomasal emptying in the calf. Res. vet. Sci. 27, 1-4. BLL, F. R. & McLAY, L. M. (1978). The effect of duodenal infusion of milk, casein, lactose and fat on gastric emptying and acid secretion in the milk-fed calf. J. Physiol. 282, BLL, F. R. & MOSTAGHNI, K. (1975). Duodenal control of gastric emptying in the milk-fed calf. J. Physiol. 245, BLL, F. R., NouRI, M. & WBBR, D.. (198). The effect of isotonic duodenal infusions of ph on gastric emptying and secretion in the calf. J. Physiol. 31, 8P. BLL, F. R. & RAZIG, S. A. D. (1973a). Gastric emptying and secretion in the milk-fed calf. J. Physiol. 228, BLL, F. R. & RAZIG, S. A. D. (1973b). The effect of some molecules and ions on gastric function in the milk-fed calf. J. Physiol. 228, BLL, F. R. & WBBR, D.. (1979). Gastric emptying and secretion in the calf on duodenal infusion of tryptophan, tryptamine and 5-hydroxytryptamine. J. Physiol. 291, BNY6, I., SiNDOR, J. & SZAB6, G. (1979). The effect of duodenal acidification on gastric circulation and function in the dog. Acta hepato-gastroenterol. 26, BLUM, A. L., KOLZ, H. R., SCHMID, P., SiUBRLI, H., LARGIADR, F. & KRJS, G. J. (1975). Studying gastric emptying in animals and man. In Proceedings ofthe Vth International Symposium on Gastrointestinal Motility, ed. VANTRAPPN, G., pp Belgium: Typoff-Press. COOK, A. R. (1977). Localization of receptors inhibiting gastric emptying in the cat. (astroenterology 72, HIRSCH, A. (1893). Untersuchungen uiber den influss von Alkali und Sdure auf die motorischen Funktionen des Hundemagens. Zentbl. klin. Med. 14, HUNT, J. N. (1956). Some properties of an alimentary osmoreceptor mechanism. J. Physiol. 132, HUNT, J. N. & KNox, M. T. (1962). The regulation of gastric emptying of meals containing citric acid and salts of citric acid. J. Physiol. 163, HUNT, J. N. & KNOX, M. T. (1969). The slowing of gastric emptying by nine acids. J. Physiol. 1,

11 DUODNAL ACID CONTROLS GASTRIC FUNCTION 341 HUNT, J. N. & KNOX, M. T. (1972). The slowing of gastric emptying by four strong acids and three weak acids. J. Physiol. 222, HUNT, J. N. & SPURRLL, W. R. (1951). The pattern of emptying in the human stomach. J. Physiol. 113, KONTURK, S. & GROSSMAN, M. I. (1965). Localisation of mechanism for inhibition of gastric secretion by acid in intestine. Gastroenterology 49, LAGRL6F, H. O., RUDWALD, M.-B. & PRMAN, G. (196). The neutralization process in duodenum and its influence on gastric emptying in man. Acta med. scand. 168, MYR, J. H., WAY, L. W. & GROSSMAN, M. I. (197). Pancreatic response to acidification of various lengths of proximal intestine in the dog. Am. J. Physiol. 219, MYLRA, P. J. (1966). Digestion of milk in young calves. I. Flow and acidity of the contents of the small intestine. Res. vet. Sci. 7, ROBINSON, J.. & WINSHIP, D. H. (1969). H+ loss, water flux and CO2 tension in the human duodenum. Clin. Res. 17, 529. RUN, S. (1968). Duodenal inhibition of gastric secretion. In The Physiology of Gastric Secretion, ed. SMB, L. S. & MYRN, J., pp Oslo: Universitets Forlaget. WALDUM, H. L. & BURHOL, P. G. (1979). The effect of duodenal acidification on plasma secretin and gastrin and pancreatic bicarbonate secretion in man. Acta hepato-gastroenterol. 26, WBBR, D.., NOURI, M. & BLL, F. R. (198). A study of the effects of meal temperature on gastric function. Pfluigers Arch. 384,