Suspensions of triglycerides in test meals as a stimulus to the duodenal. London, S.E. 1. (Hunt & Pathak, 1960).

Transcription

1 J. Phy8iol. (1964), 171, pp With 1 text-figure Printed in Great Britain THE ATON OF POTASSUM OLEATE AND POTASSUM TRATE N SLOWNG GASTR EMPTYNG BY J. N. HUNT AND M. T. KNOX From the Department of Physiology, Guy's Hospital Medical School, London, S.E. 1 (Received 14 September 1963) Fat added to food slows gastric emptying (Beaumont, 1833). t is believed that the mechanism involves the splitting of the fat in the duodenum and the stimulation of receptors sensitive to the soaps so formed (Quigley & Meschan, 1941). The possibility that the digestion products of fat circulating in the blood mediate the response has been excluded (Quigley, Zettleman & vy, 1934). The connexion between the excitation of the receptors and the reduced peristaltic action, which is held to be responsible for the slowing of gastric emptying, could be by nerves, hormones or both. n favour of the view that the slowing by fat of emptying is hormonally mediated is the finding that the feeding of fat inhibits the motility of a transplanted denervated pouch (Farrell & vy, 1926). However, the results of experiments on the motility of a pouch cannot be taken to indicate unequivocally that the corresponding slowing of gastric emptying of the intact stomach connected to the duodenum is mediated hormonally. f a hormone is released which slows gastric emptying it would be expected to stay in the circulation for several minutes at least, and its slowing influence could be tested for by subsequently administering nonfatty meals of known emptying rate. f a delaying hormone is present, the emptying of the succeeding non-fatty meal would be retarded. The present experiments were designed to test variations on this theme by using fatty meals and meals containing potassium ions, which are believed to slow gastric emptying by stimulating duodenal osmoreceptors (Hunt & Pathak, 196). Suspensions of triglycerides in test meals as a stimulus to the duodenal receptors are unreliable, as such emulsions are usually unstable in the stomach. To overcome this difficulty test meals containing potassium oleate have been used in the present work. METHODS Three types of meal were used: (1) 1 mn sodium citrate; (2) 1 mn potassium oleate; and (3) 1 mn potassium citrate.

2 248 J. N. HUNT AND M. T. KNOX To make 1 1. of potassium oleate meal, 2-8 g of oleic acid was boiled with 1 ml. of 1 mn-koh solution. After 4 ml. of distilled water had been added, the mixture was again heated to boiling point and then diluted with distilled water to 1 1. Potassium oleate was used because it is more soluble than sodium oleate. Where indicated, 3 ml./l. of a saturated solution of phenol red was incorporated in the sodium citrate meals. This is thought to have no action on gastric emptying (Hunt, 1956). Procedure. The subject came fasting to the laboratory in the morning, and after the stomach had been washed out with 25 ml. of tap water, 75 ml. test meal at 37 was given in about 75 sec by tube into the stomach from a funnel at a fixed height. (For two small women the volume of the meals was reduced to 6 ml.) Three minutes after the beginning of instillation recovery of the gastric contents was started. As soon as the recovery was complete the next meal was given. This cycle of instillation and recovery was repeated five times in succession, the whole series taking about 25 min. There were fifteen series in four subjects. A second group of subjects was studied in the same way, except that the recovery of the meals was not begun until 7 min after instillation, and the cycle was repeated only 3 times. t is known that a test meal containing 1 mn sodium citrate leaves the stomach about twice as quickly as water (Hunt & Knox, 1962). Such a meal can therefore be used as a control in comparisons designed to show up minor degrees of inhibition of gastric emptying, which might not be apparent with control meals which emptied slowly by virtue of their own composition. The meals of 3 min duration were grouped in three series: Series 1 Series 2 Series 3 Meal (1) Na cit. 1* Na cit. 1 Na cit. 1 (2) Na cit. 1 K ol. 1 K cit. 1 (3) Na cit. 1 Na cit. 1 Na cit. 1 (4) Na cit. 1 K ol. 1 K cit. 1 (5) Na cit. 1 Na cit. 1 Na cit. 1 * All concentrations expressed as millinormal; cit. = citrate; ol. = oleate. For the meals of 7 min duration, the first three meals only in each series were given. To see whether each recovery was complete, the first, third and fifth meals each contained phenol red as a marker (Hunt & Knox, 1962) while the second and fourth meals were colourless. Any corrections for incomplete recovery of the volumes of meal could then be made after colorimetric estimation of phenol red in the recoveries. n practice, the corrections were so small as to be negligible. Method of analysis of results. Under our conditions, the volumes of each type of meal recovered varied from subject to subject. Since sodium citrate test meals were common to each series, the actual volumes of meal remaining were expressed as percentages of the mean volume of all the sodium citrate meals in the series for each individual. The means of these percentages were then calculated for the group of subjects. The details of the calculation can be seen in Table 1. RESULTS Figure 1 shows the combined results of 114 recoveries from eight subjects. Series 1. There was an increase in the mean volumes recovered with the last two successive meals both with the 3 and 7 min series containing only sodium citrate meals. Series 2. The volumes of potassium oleate meals recovered were about 4-5% greater than the volume recovered after the preceeding sodium

3 FAT AND GASTR EMPTYNG S O v g o 5 ora +1 H Oo_ +l in- 1 O - O o : OOo< o - E o:-1 S -_ 6 O a +l O o t- O O - M-4 -_ -*.* O i i t O * *q a*. +l O 1* b i ~i rq O 1 t- o c: i-e- ; Q;4 o co cto cc enr q *4 - (M N O aq O O 't- 1 -xt i1 o > oo 1o 4 1 O i,oxolt' m _t c O Nn to O OO <D = t-oo_ i OO 4-4 FH tl Z 1111 O to ~ t O O o o Z co o 4 --m=m -o -- Nc a) *r* ntc to Atb sts<4 * ~ OO11i '-4 " "< to 1 t4~.ji otoxm i xo 1- S>cx t = to X 1nn <rwc11*cl 4-4 b4 t 411: OQ pl- LO V- -4 = c 1t O111o1 _ cs _-4 cs km a] 1 r 1 rto11 11 O 1O1 1o1. ~~~~ ~~~~ o %)Z * P ~.- S QD w w O - " Z 4Q $ ZWW X - 4

4 25 - J. N. HUNT AND M. T. KNOX r ±5 ±2 ±2 ±3 ±3 NaNa Na Na Na v Series 21 w 15 c o 1 ti 4) 5 1S 82 ±8 Na ±9 ±3 Na Na (a a, U a,1 {J _ o c ± 2 ±11 ±4 ±9 ± 3 ± 8 ± 1±E Na K Na K Na Na K Na ( Series > OOF +1_ t. 8 5 n ±6 ±2 1±5 Na K ina 127 ± 2 KG 1 ± 2 Na Series Na ±7 ± 11 K Na Fig. 1. Recoveries of sodium citrate meals, potassium oleate meals and potassium citrate meals all expressed as percentages of mean recovery of sodium citrate meals (i.e. control)., s.e. of mean. citrate meals. n the 3 min series, the percentage recoveries of sodium citrate meals following the 1 mm potassium oleate were almost identical with the corresponding meals (3 and 5) in the first series of five sodium

5 FAT AND GASTR EMPTYNG o q o *4 m +l +1 +1,- te- _Z oo ~ =a Q& 5 c = 1o ( _-. *b cl = o- 1-._ ro t- cw.4.5 (~ tz k-()- 1- o- co o- - cd al -4 Wo afro -4 -( A(: c Z:q -4b H 4r- oo _ O Ud4 o Q >.4-4 O GS O Xm c O_ - s: a a, p4 ~ -,: oc o UV UO oo O l _ tox _ c 1,,: q" "1* D co " " i 14 X a O t O 14 O O Ut O) lll (M all to a N "N t- P-_q Oko 4 c o to ".* = xo * " r- u: " -a m co Z mo O< m ooo b 1 1e t M E o 1Z1 t 41* o*c H es llq lil 11 1t M A -4 4 p P x. O as e B -4 (OD GD e co o Z> 4.eof w o -4._l - co as c ee m -4 _

6 252 J. N. HUNT AND M. T. KNOX citrate meals. n the 7 min series the percentage recovery of the third meal was actually less than the corresponding meal in the series of three sodium citrate meals. Series 3. The mean percentage recoveries of 1 mn potassium citrate meals were about 2o/ more than those of the sodium citrate meals. The mean percentage recoveries of sodium citrate following potassium citrate are in each instance less than the corresponding recoveries of sodium citrate following sodium citrate. The details of the results presented in the figures are shown in Tables 1 and 2. DSUSSON ontrary to expectation there was no evidence in the results of the present experiments to suggest that a hormone which slows gastric emptying was released by meals containing either 1 mn potassium oleate or 1 mn potassium citrate. Potassium chloride in high concentrations is thought to activate the duodenal osmoreceptors (Hunt & Pathak, 196) but the concentration of potassium in the 1 mn potassium oleate is below the threshold for this effect of the potassium ion. Under the conditions employed the existence of a hormone capable of slowing gastric emptying has not been demonstrated. f the slowing of emptying of potassium oleate or of potassium citrate meals is mediated by a hormonal mechanism, then the hormone concerned must have a very short half-life. n view of the fact that the response to different types of test meal is immediate, and specific to the meal given, it would seem more likely that a nervous reflex mechanism is responsible for controlling the rate of emptying in these meals. t is interesting that the response to the oleate meals is so short-lived, which presumably implies that the receptors responding to the oleate have only a brief action. The conclusion that nervous reflexes are probably involved is consistent with the finding that vagotomy in man (Waddell & Wang, 1953) and sympathectomy in dogs (erqua, 1935) reduces the slowing of emptying produced by fats. SUMMARY 1. Test meals of 1 mn sodium citrate, 1 mn potassium oleate and 1 mn potassium citrate in six series of various combinations were given in quick succession to eight subjects. After either 3 or 7 min, the meal remaining in the stomach was withdrawn, and its volume measured. 2. Potassium oleate and potassium citrate meals emptied at a significantly lower rate than sodium citrate meals. 3. Potassium oleate and potassium citrate meals had no inhibitory influence on the emptying of a sodium citrate meal immediately following.

7 FAT AND GASTR EMPTYNG 253 t was concluded that either the slowing of gastric emptying by fat was not mediated by a hormone, or it was mediated by a hormone with a short half-life. REFERENES BEAUMONT, W. (1833). Experiments and Observationm on the Gastric Juice and the Physiology of Digestion. Plattsburgh: F. P. Allen. ERQUA, S. (1935). The part played by the splanchnic innervation in emptying of the stomach. J. Physiol. 84, FARREL, J.. & vy, A.. (1926). Motility of transplanted gastric pouch. Amer. J. Physiol. 76, HUNT, J. N. (1956). Some properties of an alimentary osmoreceptor mechanism. J. Physiol. 132, HUNT, J. N. & PATHAK, J. D. (196). The osmotic effects of some simple molecules and ions on gastric emptying. J. Physiol. 154, 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, QUGLEY, J. P., ZETTLEMAN, H. J. & vy, A.. (1934). Analysis of the factors involved in gastric motor inhibition by fats. Amer. J. Physiol. 18, QUGLEY, J. P. & MESHAN,. (1941). nhibition of the pyloric sphincter region by the digestion products of fat. Amer. J. Physiol. 134, WADDEL, W. R. & WANG,.. (1953). The effect of vagotomy on gastric evacuation of high fat meals. J. appl. Physiol. 5, Physiol. 171