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Pentagastrin Induced Motility Pattern in the Human Upper Gastrointestinal Tract Is Reversed by Proglumide

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Pentagastrin Induced Motility Pattern in the Human Upper Gastrointestinal Tract Is Reversed by Proglumide Gut: first published as 10.1136/gut.25.9.953 on 1 September 1984. Downloaded from Gut, 1984, 25, 953-956 Pentagastrin induced motility pattern in the human upper gastrointestinal tract is reversed by proglumide J F ERCKENBRECHT, J CASPARI, AND M WIENBECK From the Department of Internal Medicine D, University of Dusseldorf, Dusseldorf, FR Germany SUMMARY The effects of pentagastrin and the putative gastrin antagonist proglumide on interdigestive motility of the upper small bowel were studied in a randomised double blind study in 10 healthy human volunteers. Intraluminal pressures were recorded manometrically in the duodenum and jejunum for five hours. Sixty minutes after starting a pentagastrin infusion (0.15 ,ug/kg/h) either placebo or proglumide was infused intravenously. Pentagastrin converted the normal interdigestive motility to irregular motor activity, while proglumide restored the periodic fasted pattern. We conclude that gastrin is a likely candidate involved in the conversion of the fasted to the fed motility pattern in the human upper gut. In the fasted state, motility of the stomach and small Methods intestine of man is characterised by periodic activity of the interdigestive migrating motor complex SUBJECTS (MMC). 1-4 Immediately after feeding, gastro- Ten healthy male volunteers (mean age 25±2 intestinal motility becomes irregular.4 In the con- (x ± SD) years) were examined in a double blind, version of the interdigestive to the digestive motility randomised, crossover study after giving informed pattern not only neural mechanisms,5 but also consent. http://gut.bmj.com/ gastrointestinal hormones, particularly chole- Intraluminal pressures were measured mano- cystokinin (CCK) and gastrin, appear to be metrically by a triple lumen polyvinyl tube. The involved.i8 This is illustrated by recent observa- inside diameter of the three catheters was 0*8 mm tions, showing that endogenous gastrin interrupts each. The distal side openings of the three catheters the migrating motor complex in an autotrans- were 20 cm apart. Beyond the side openings the planted, denervated fundic pouch.9 catheters were occluded by a stainless steel plug. At Proglumide inhibits the CCK stimulated secretion their proximal ends the catheters were connected to on October 7, 2021 by guest. Protected copyright. of dispersed pancreas acini, i) and also the motor pressure transducers. Pressure events were recorded response of isolated smooth muscle cells after via a bridge amplifier (Hellige TF 19) on a direct stimulation by CCK octapeptide. "l These and other writing polygraph (Hellige P 31). The pressure findings'2 13 support the concept of proglumide transducers and the catheters were continuously being an antagonist of CCK and gastrin at the perfused by a low compliance pneumohydraulic receptor site. pump'5 at a rate of 9 ml H20 h-1. The present study examines the effect of penta- Before each experiment the volunteers were gastrin infused at a dose that produces a rise in fasted for 10 hours. The manometric tube was gastric acid secretion similar to the increased serum introduced through the mouth and positioned under gastrin seen after feeding,'4 and its combination radiographic control with its side openings into the with the putative gastrin antagonist proglumide on duodenum and jejunum. The initial basal the interdigestive motility of the human upper registration was continued, until the first activity gastrointestinal tract. front of the MMC had passed the duodenum. Then the volunteers received pentagastrin 0.15 ,ug/kg bodyweight/h by intravenous infusion for five hours. Address for correspondence: Dr J F Erckenbrecht, Dept of Internal Medicine D. University of Dusseldorf, Moorenstrasse 5, D-4000 Dusseldorf 1. FR Sixty minutes after starting the pentagastrin Germany. infusion, in addition, either proglumide or the same Received for publication 18 November 1983 volume of placebo solution (normal saline) was 953 Gut: first published as 10.1136/gut.25.9.953 on 1 September 1984. Downloaded from 954 Erckenbrecht, Caspari, and Wienbeck infused for four hours in a double blind fashion. The with pentagastrin + placebo), and to 1-7±0-4/4 h in dose of proglumide was 400 mg as an initial 5 ml the jejunum (p<0.01). bolus followed by an infusion of 500 mg/h. Serum proglumide concentrations were The order of the experiments (pentagastrin + determined 30 minutes and 240 minutes after the proglumide or pentagastrin + placebo) was start of the proglumide infusion. After 30 minutes randomised. After the start of the additional proglumide infusion serum concentrations ranged infusion (proglumide or placebo), the pressure from 0 58 ,ug/ml to 28-26 (median 3.8), they were recordings were continued for four hours. The less than 2 ,ug/ml in seven subjects. Two hundred control experiment with either placebo or and forty minutes after the beginning of the proglumide followed within one week. Serum proglumide infusion serum concentrations ranged proglumide concentrations were determined by from 058 gg/ml to 39 2 ,tg/ml (median 5 4), they gas chromatography.'6 were less than 2 ,ug/ml in seven subjects. There was We evaluated the number of activity fronts of the no clear rolationship between the serum proglumide MMC in the duodenum and jejunum. Differences concentrations 30 or 240 minutes after starting the between the proglumide and placebo experiments proglumide infusion and the number of activity were tested for significance by Student's t test for fronts of the MMC. paired data. Discussion Results In the interruption of cyclic interdigestive motility The results are given in Figures 1 and 2. Penta- after feeding not only neural mechanisms, but also gastrin 015 ,ug/kg bodyweight/h interrupted the gastrointestinal hormones appear to be involved. normal interdigestive motility pattern of the upper Endogenous gastrin9 and exogenous administration intestine (Fig. 1). During pentagastrin infusion the of CCKX have been found to convert the fasted to number of activity fronts in the duodenum and the fed motility pattern which is characterised by jejunum was reduced to 0 4±0 2 (x ± SEM/4 h). apparently irregular contractile activity. Irregular contractions prevailed (Fig. 3). The present study shows that the administration Infusion of proglumide in addition to pentagastrin of pentagastrin in a dose which stimulates gastric restored the normal periodic interdigestive motor acid secretion to a similar extent as the postprandial activity (Fig. 2). The mean period of the MMC was gastrin rise interrupts the regular periodic inter- approximately two hours. The number of activity digestive motility in the upper gastrointestinal tract. http://gut.bmj.com/ fronts of the MMC increased to 2*0±0*5/4 h Activity fronts of the MMC are absent or their (x ± SEM/4 h) in the duodenum (p<0.02 compared number clearly reduced. The motility pattern Pentagastrin + Placebo D t - ' l = D E 1 6 on October 7, 2021 by guest. Protected copyright. 2 JD r. 7 JD t D l ---A ". l 5D , f I, --4 J 4_ n- -- -t 10 0 60 120 180 240 0 60 120 180 240 Fig. Effect ofpentagastrin (min) (min) (0 15 dLglkglh) on interdigestive D = Duodenum - No motor activity motility ofthe duodenum (D) J = Jejunum - Irregulor motor activity and jejunum (J) in 10 healthy Regular motor activity resembling volunteers. phase III of the MMC Gut: first published as 10.1136/gut.25.9.953 on 1 September 1984. Downloaded from Pentagastrin-induced motility pattern is reversed by proglumide 955 Pentagastrin + Proglumide 1 | * 1 D Jl * , 4D Si J * Fig. 2 Effect ofpentagastrin (0.15 ,uglkglh) and proglumide 10D == (400 mg as a bolus followed by 0 60 120 180 240 0 60 120 180 240 500 mglh) on interdigestive (min) (min) motility ofthe duodenum (D), and jejunum (J) in 10 healthy D = Duodenum J = Jejurum IIII Phases of the interdigestive volunteers. motor complex (MMC) brought about by pentagastrin administration is the hypothesis of proglumide being a gastrin- and characterised by irregular motor activity. These CCK-receptor antagonist. 1"'3 findings lend support to the idea that the serum Proglumide and pentagastrin have direct actions gastrin rise after feeding is involved in the on the gastrointestinal smooth muscle cell" 17 18 in conversion of the interdigestive to the digestive that they appear to act on CCK and gastrin motility pattern in the upper gUt.6 7 9 receptors. In these observations pentagastrin and Additional infusion of proglumide restores the gastrin were shown to increase myoelectrical and interdigestive motility pattern which has a mean motor activity of the stomach, while proglumide period between activity fronts of the MMC of inhibited myoelectric and motor activity in the http://gut.bmj.com/ approximately two hours. These findings support isolated stomach and ileum.'8 It is unlikely that 40 20 D _ f on October 7, 2021 by guest. Protected copyright. m~~~~~~~~~~~~~~~ l -& 0 Before d infusiononm I40 401 X t B B 1.U Pentogastnrn + plocebo 1 min 40 20 Fig. 3 InterdigestiveD motility 01 ii-_ ofthe duodenum (D) and jejunum (J) before and during pentagastrin + placebo and Pentagastrin + proglumide 1 min pentagastrin + proglumide D = Duodenum infusion. J = Jejunum Gut: first published as 10.1136/gut.25.9.953 on 1 September 1984. Downloaded from 956 Erckenbrecht, Caspari, and Wienbeck changes in gastric acid secretion play a major role in activity of small intestine of the dog. Am J Physiol the motor effects of pentagastrin and proglumide, as 1974; 227: 425-9. (a) in animal experiments pentagastrin alters small 8 Schang J-C, Kelly KA. Inhibition of canine inter- motility even if gastric secretions are digestive proximal gastric motility by cholecystokinin intestinal octapeptide. Am J Physiol 1981; 240: G217-20. diverted from the duodenum7 and (b) proglumide 9 Thomas PA, Schang J-C, Kelly KA, Go VLW. Can has only weak actions on gastric acid secretion.19 endogenous gastrin inhibit canine interdigestive gastric motility? Gastroenterology 1980, 78: 716-21.
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