Gastrin Pentapeptide Decreases Canine Gastric Transmural Pressure

67:1139-1142, 1974 Copy right© 1974 by The Williams & Wi lkins Co.

Vol. 67, No.6 Printed in U.S.A.

GASTROENTEROLOGY

GASTRIN PENTAPEPTIDE DECREASES CANINE GASTRIC TRANSMURAL PRESSURE BRUCE G. WILBUR, M.D .,

AND

KEITH A. KELLY, M.D.

Mayo Clinic and Mayo Foundation, and the Mayo Medical School, Rochester, Minnesota

In 4 conscious, fasted dogs , the transmural pressure of the distended stomach was measured continuously for 75 min, while 154 mM NaCl (0.8 ml per min) was infused intravenously. Identical experiments were repeated on 3 different days, except that gastrin pentapeptide (GPP), 0.1 f.lg per kg per min, was added to the NaCl infusion from the 15th to the 45th min. The mean gastric transmural pressure of about 11 em of H 2 0 varied only slightly when NaCl alone was infused. Slow phasic changes in pressure occurred with a frequency of three to five per min and an amplitude of 3 to 11 em of H 2 0. Within 2 min after onset of the GPP infusion, mean pressure decreased in all experiments in all dogs, and it remained low throughout the infusion (mean , about 6 em of H 2 0). Phasic changes in pressure were nearly abolished by GPP. After GPP infusion was stopped, mean pressure and phasic changes gradually returned to control by 30 min. This experiment shows that gastrin pentapeptide decreases gastric transmural pressure in the distended stomach. Hunt and Ramsbottom 1 found that gastrin, a stimulant of gastric contractions during fasting, actually slows gastric emptying of liquids. The mechanism of the slowing has been investigated, but remains unclear. 1-3 Our hypothesis is that gastrin decreases gastric transmural pressure in the distended stomach, thus weakening the driving force behind gastric emptying . An abstract of this work has been published. 4

Methods Four healthy mongrel female dogs, 10 to 12 kg in weight, were used. They were alert and conscious during all experiments and had been

fasted at least 18 hr. They were accustomed to the passage of an oral gastric tube. In control experiments, performed once in each dog, gastric t ransmural pressure was measured during gastric distention to 500 ml with a flaccid plastic bag of capacity greater than 500 ml (gastric transmural pressure is that pressure due solely to contractions of the gastric wall). The pressure was recorded as the difference between the simultaneously measured pressures inside and outside the gastric wall. The pressure in the stomach was measured via a fluid-filled catheter connecting the intragastric plastic bag to a pressure transducer (Statham P23Dd). The pressure outside the stomach was measured using a sterile, plastic catheter (internal diameter, 1 mm) placed intraperitoneally and attached via a three-way connector to a second transducer positioned adjacent to the first. A continuous infusion of 154 mM NaCl at 0.1 ml per min was given through the third channel of the connector to keep the intraperitoneal catheter patent. The resistance of the catheter to the infusion was so low that the infusion did not measurably increase the pressure recorded from the catheter. The flaccid plastic bag was inserted through

Received December 27, 1973. Accepted June 17, 1974. Address requests for reprints to: Dr. Bruce G. Wilbur. c/o Section of Publications, Mayo Clinic, Rochester, Minnesota 55901. This investigation was supported in part by Research Grarit AM-2015 from.the National Institutes of Health, United States Public Health Service. Valuable critique from Dr . C. F. Code is gratefully acknowledged. 1139

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Vol. 67, No . 6

WILBUR AND KELLY Dog 8

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FIG. 1. Gastrin pentapeptide decreases gastric transmural pressure. In tests in which NaCl alone was infused, each point is mean pressure over 3 min. In tests in which gastrin pentapeptide (pentagastrin) was added to NaCl, each point is overall mean of three 3-min mean pressures from three separate experiments. Curves based on overall means are typical of individual experiments.

the mouth of the dog and into the stomach, via a bite block, and was distended with water at 37 .5°C to 500 ml during a 3-min interval. A continuous record of the gastric transmural pressure was obtained for 75 min (five sequential 15-min periods) by feeding the electric signals from the two transducers, which measured intragastric and extragastric pressures, into a differential amplifier. The amplifier, in tum, fed the difference between the two signals into a servo recorder (Heathkit) that recorded the transmural pressure at a chart speed of 3 inches per min. The apparatus was calibrated before and after each experiment by means of water manometers . Mean pressure during 3-min intervals was calculated by measuring the area under sequential 3-min curves . Mean pressure for the five sequential 15-min periods was also determined. Throughout the 75 min, 154 mM NaCl was infused intravenously into a forelimb vein at a rate of 0.8 ml per min. Identical experiments were repeated on each dog on each of 3 different days, except that gastrin pentapeptide, 0.1 f.lg per kg per min , was added to the NaCl infusion from the 15th to the 45th min (second and third 15-min periods). In another set of experiments, performed once in each dog, the flaccid plastic bag was inserted into the stomach and distended with 500 ml of a 5.0% aqueous solution of sodium diatrizoate (Hypaque). The position of the distended bag in the stomach was observed fluoroscopically over a 5-min period while 154 mM

TABLE

1. Effect of gastrin pentapeptide (GPP) on gastric transmural pressure Mean gastric transmural pressure"

Intravenous infusion

0- 15 min

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NaCl (154 mM) GPP' and NaCl (154 mM)

9.8 10.7 l1 .8 l1.8 10.6 10.8 6.2< 5.F 6.9< 10.0

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NaCI, 0.8 ml per min, was infused intravenously. Gastrin pentapeptide, 0.1 f.lg per kg per min , was then added to the infusion, and fluoroscopic observation was continued for another 5 min.

Results Control. The mean gastric transmural pressure of about 11 em of H 2 0 changed little when NaCl alone was infused intravenously (fig.l, table 1). Slow phasic changes in pressure occurred during the entire 75 min at a frequency of three to five per min

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GASTRIN PENTAPEPTIDE RELAXES STOMACH

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FIG. 2. A, mean gastric transmural pressure and phasic changes in pressure are unchanged during intravenous infusion of 154 mM NaCl, 0.8 ml per min, for 75 min. B, gastrin pentapeptide (GPP) promptly decreased mean gastric transmural pressure and inhibited phasic changes in pressure. After GPP infusion was stopped, mean pressure and phasic changes gradually returned to control.

and an amplitude of 3 to 11 em of H 2 0 (fig.

Gastrin pentapeptide. The mean gastric transmural pressure and the frequency and Fluoroscopic examination of the stom- amplitude of the phasic changes in presach showed that the intragastric plastic sure during the initial 15 min when NaCl bag used to distend the stomach occupied alone was infused did not differ from the the gastric fundus and corpus (but not the controls (figs. 1 and 2B, table 1). Within 2 min after the start of the infusion of gastrin antrum) in all 4 dogs. 2A).

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WILBUR AND KELLY

pentapeptide (overall mean 1.5 min) , a decrease in mean transmural pressure and in amplitude of phasic changes in pressure occurred in all dogs in all experiments (figs. 1 and 2B, table 1). Mean pressure remained low (about 6 em of H 2 0) throughout the infusion of gastrin pentapeptide, and phasic changes were nearly abolished. After gastrin pentapeptide infusion was stopped, mean pressure and phasic changes gradually returned to control during the ensuing 30 min (figs. 1 and 2B, table 1). The infusion of gastrin pentapeptide did not alter the position of the plastic bag in the fundus and corpus of the stomach. Discussion Our experiment shows that gastrin pentapeptide decreases gastric transmural pressure in the distended stomach. The exact site of action and mechanism by which gastrin pentapeptide decreases gastric transmural pressure are unknown. The rapid onset of its action (within 2 min in all experiments) suggests that gastrin pentapeptide acts directly on structures in the gastric wall. However, it may act

indirectly by stimulating gastric secretion of HCl, which would, in turn, either activate an enterogastric reflex or release an enteric hormone, such as secretin, both of which might then inhibit gastric motor activity. Additional work is needed. Cannon and Lieb 5 showed that the vagal nerves aid in the accommodation of the stomach to ingesta, a phenomenon they called " receptive relaxation ." These experiments now demonstrate that gastrin pentapeptide also facilitates accommodation of the stomach to distention. REFERENCES 1. Hunt JN, Ramsbottom N: Effect of gastrin II on gastric emptying and secreti on during a test meal. Br Med J 4:386- 387, 1967 2. Dozois RR, Kelly KA: Effect of a gastrin pentapeptide on canine gastric emptying of liquids. Am J Physiol 221:113-117, 1971 3. Cooke AR, Chvasta TE, Weisbrodt NW: Effect of pentagastrin on emptying and electrical and motor activity of the dog stomach. Am J Physiol 223:934-938, 1972 4. Wilbur BG, Kelly KA: Gastrin pentapeptide decreases canine gastric transmural pressure (abstr). Gastroenterology 64:823, 1973 5. Cannon WB, Lieb CW: The receptive relaxat ion of the stomach. Am J Physiol 29:267-273, 1911