GASTRONTROLOGY opyright 1967 by The Williams & Wilkins o. Vol. 52, No.2, Pat 1 Printed in U.S.A. PRSN OF A GASTR MOTOR-STMULATNG PROPRTY N DUODNAL XTRATS JOHN. BROWN, PH.D. Department of Physiology, University of British olumbia, Vanouver, British olumbia, anada Alkalinization of the duodenum will produe inreased motor ativity from transplanted fundi pouhes. Brown et al. l have suggested that the inreased motor ativity of the fundi pouhes ould be due to the inhibition of the release of holeystokinin-panreozymin or release of a stimulatory agent from the duodenal muosa. This study was undertaken to test the latter hypothesis, and ommerially available duodenal extrats have been reexamined for fundi pouh-stimulating properties. Methods Five dogs weighing between 15 and 2 kg were used in this study. Four were prepared with a transplanted fundi pouh and one with a Bikel pouh (sympathetially and vagally denervated), and all animals had a short Mann-Bollman fistula opening into the duodenum, about 2 to 3 m below the pylorus. Motility reording. Gastri pouh motility was measured using a low pressure Statham transduer, and ontrations were monitored on a Gilson pen reorder.1 Duodenal pressure hanges were measured using go-gauge intramedi polyethylene tubing annulae introdued into the duodenum via the Mann-Bollman fistula and attahed to a seond low pressure Statham transduer. n some instanes, duo- Reeived August 29, 1966. Aepted Otober 5, 1966. Address requests for reprints to: Dr. John. Brown, Department of Physiology, University of British olumbia, Vanouver 8, British olumbia, anada. This investigation was supported by Grant MA- 1972 from the Medial Researh ounil of anada and by a gift of panreozymin from the Boots Pure Drug ompany, Ltd., ngland. The tehnial assistane of Miss Jill Dryburgh is appreiated. 225 denal ph was also reorded by the method previously desribed. 1 The following measurements were obtained from the pen reordings of the gastri pouh pressure hanges: (a) frequeny of ontrations-the number of pressure waves per 1- min period; (b) perentage of ativity-the perentage of the 1O-min period that pressure wave ativity was observed ; and () total amplitude-the summation of the heights of all the waves during a 1O-min period, measured in millimeters of merury. Figure 1 shows an atual experimental reording. Four duodenal extrats were used: seretin and panreozymin as prepared by the Boots Pure Drug ompany (ngland), and seretin and eekin as prepared by Vitrum (Sweden). A ontrol period of 3 to 6 min was obtained prior to the intravenous infusion of duodenal extrats, during whih time the pouhes demonstrated regular spontaneous ontrations or motor ativity was absent. All intra venous infusions were performed over a period of 1 to 2 min. The number of observations on eah individual animal is given in table 1. Results ntravenous infusion of Boots seretin. ntravenous infusion of Boots seretin in doses of 2 to 3 units per kg produed no signifiant hange in frequeny of ontrations (fig. 2, P >.5), in perentage of motor ativity (fig. 3, P >.4), or in total amplitude (fig. 4, P >.8). ight observations were made on 3 animals. ntravenous infusion of Vitrum seretin. ntravenous infusion of Vitrum seretin in doses of 2 to 3 units per kg produed no signifiant hange in frequeny of ontrations (fig. 2, P >.1), in perentage of motor ativity (fig. 3, P >.1), or in total amplitude (fig. 4, P >.5). ight observations were made on 3 animals.
226 BROWN Vol. 52, No.2, Part 1 r: a. D a - ro 4 Units PZN r: -...tl...,.j.j,..j)j. 1: [ JJJJLLJLl o 1 2 Time in Minutes..., " D (n (n.., D r 3 3 FG. 1. An atual ontinuous experimental reording showing the experimental pattern. The upper traing shows duodenal pressure hanges measured by means of a atheter introdued via the Mann-Bollman fistula into the duodenum. The lower traing shows transplanted fundi pouh pressure hanges. The Boots seretin (SN) and Boots panreozymin (PZN) were infused intravenously over a -min period. :r: TABL 1. Number of observations on eah individual animal Dog identifiation Type of fundi pouh No. of infusions of test material Boots Vitrum Boots seretin seretin ozymin panre- Vitrum eekin -------- Pr... Bikel 5 2 Pa....... Transplant 4 Lo... Transplant 3 3 4 2 Jo.. Transplant 3 3 3 3 Re... Transplant 2 2 2 2 ntravenous infusion of Boots panreozymin. ighteen observations were made on 5 animals. The frequeny of ontrations was inreased from a resting level of 7. ± 1.4 to 24.8 ± 2. ontrations per 1 min (fig. 2) by the infusion of 1. to 2. units per kg of panreozymin over 1 min. These data represent a signifial).t inrease in frequeny of ontrations (P <.1). The perentage of ativity was inreased from 12.7 ± 2.5 to 54.3 ± 5.3 per 1 min, a signifiant inrease (fig. 3, P <.1). Likewise, the total amplitude was signifiantly inreased, from 162 ± 56 to 893 ± 122 mm Hg in 1 min (fig. 4, P <.1). ntravenous infusion of Vitrum eekin. Ten observations were made on 5 animals. ntravenous infusion of eekin,.6 to 2. units per kg, produed no signifiant hange in frequeny of ontrations (fig. 2, P >.3), in perentage of motor ativity (fig. 3,
Febl'uary 1967 GASTR MOTOR-STMULAT NG PROPRTY 227 28 en T :; 2. Q 2 i;. 16,Q <:; 12 1:: 8 - OJ z N U "" a. u g <J) g e <J) e U m U :> u m u :; : 8 '8 5 FG. 2. Mean inrease in frequeny of ontrations of pouhes in response to Boots seretin and panreozymin and Vitrum seretin and holeystokinin-panreozymin (eekin). The standard error is indiated by the bars above and below the mean. P >.3), or in total amplitude (fig. 4, P >.3). Disussion The observations by Brown et au that a period of inreased motor ativity in transplanted fundi pouhes followed alkalinization of the duodenum aused these authors to suggest two possible mehanisms of ation. Alkalinization was either inhibiting the release of holeystokinin-panreozymin from the duodenum or releasing a stimulatory agent for fundi pouh motor ativity. The former hypothesis was indiretly supported by the work of Johnson and Magee 2 and Johnson et al.,3 who demonstrated t hat duodenal extrats ontaining holeystokinin and panreozymin ativity will inhibit gastri motor ativity in the dog and man. The results presented here, however, support the hypothesis that alkalinization auses the release of a stimulatory agent for fundi pouh motor ativity. Neither of the seretin preparations employed produed signifiant hanges in pouh ativity. llis (personal ommuniation) has "' 6 2 5 Q 4. 3 '5 n «2 '., 1 ' a.. += e '2 "' 8 &l =t t; (/J :> z N a.. 2 8 <D "" o e g o > FG. 3. Mean inrease in perentage of motor ativity in the pouhes in response to Boots seretin and panreozymin and Vitrum seretin and holeystokinin-panreozymin (eekin). The standard error is indiated by the bars above and below the mean. 1 9 ' ' 2 a.. 7 Q > 6-5 -- 4 ' :S i. «3 ' ; 2 1 t; z N "" a.. '2 g g '2 "' "'!: <D <D :> 8 FG. 4. Mean inrease in total amplitude of ontrations in the pouhes in response to Boots seretin and panreozymin and Vitrum seretin and eholeystokinin-panreozymin (ekin). :>
228 BROWN Vol. 52, No.2, Part 1 1 1..,..--', ) ' 4. i l - " ' _ " ' -., ", " " ' _. _ " ' ' ' '., '.... - Jt 1 o\ o 1 -' ' ' ' -' -' '-'.' ' 1 ' 1' ' '* ' + - 1 ",, _ " t - 1 -K - PZN =5 5[ '' ) J 1 J... ' 1. J.. M, W.,. +..,... A -, \..--,\-o o 1 2 3 Time in Minutes FG. 5. A ontinuous experiment showing transplanted gastri pouh pressure hanges. K represents the intravenous infusion of.6 unit per kg of holeystokinin-panreozymin over a -min period. The spontaneous ativity is inhibited. PZN represents the infusion of 2. units per kg of Boots panreozymin (orresponding to.6 unit per kg of holeystokinin). Note the burst of motor ativity from the transplanted pouh. assayed Boots seretin for serotonin and found "in the order of.4 p.g per unit of seretin." Johnson and Magee 2 demonstrated that serotonin was without effet on denervated fundi pouhes in the dog, even at levels 5 times the physiologial dose. J orpes and MutV have reently assayed the Boots panreozymin for holeystokinin ativity and have reported a level of.3 vy dog unit of holeystokinin per mg of extrat. Figure 5 shows that the intravenous infusion of a quantity of eekin, orresponding to a dose of panreozymin, whih stimulates gall bladder ontration and inreases motor ativity in these pouhes, is without stimulatory effet. Thus it would appear that neither serotonin nor holeystokinin is the humoral agent produing this response, and that the preparation of the purer eekin from duodenal extrats results in the removal of this gastri motor ativity stimulant. The absene of the inhibitory ation on fundi pouh motility by eekin in these experiments appears to onflit with the work of Johnson and Magee. 2 nhibition was not demonstrated statistially beause, in these studies, the resting ativity of the fundi pouhes was small and frequently absent. However, figure 5 shows a good example of the inhibitory ation of eekin. Attempts are being made to separate this motility-stimulating property from the panreozymin ativity and to determine whether this stimulatory ation is onfined to the stomah or ats throughout the whole of the gastrointestinal trat. Summary Duodenal extrats have been examined for gastri motor-stimulating properties. Seretin as prepared by Boots Pure Drug ompany and Vitrum and eekin by Vitrum do not stimulate fundi pouh motor ativity. The panreozymin of Boots shows powerful fundi pouh motor-stimulating properties. This is not due to the holeystokinin-panreozymin ontent of
February 1967 GASTR MOTOR-STMULATNG PROPRTY 229 this material. The presene of a separate "motor-stimulating property" is suggested. RFRNS 1. Brown, J.., L. P. Johnson, and D. F. Magee. 1966. ffet of duodenal alkalinization on gastri motility. Gastroenterology 5: 333-339. 2. Johnson, L. P., and D. F. Magee. 1965. holeystokinin-panreozymin extrats and gastri motor inhibition. Surg. Gyne. Obstet. 121: 557-562. 3. Johnson, L. P., J.. Brown, and D. F. Magee. 1966. ffet of seretin and holeystokininpanreozymin extrats on gastri motility in man. Gut 7: 52-57. 4. Jorpes,., and V. Mutt. 1966. holeystokinin and panreozymin, one single hormone? Ata Physiol. Sand. 66: 196-22.