JOURNAL
OF SURGICAL
23, 25-30 (1977)
RESEARCH
Release of Vasoactive
Intestinal Peptide Osmotic Stimuli
(VIP) by Intraluminal
AMIN M. EBEID, M.D. ,PETER B. SOETERS, M.D. ,PHILLIP JOSEF E. FISCHER, M.D. Departmeni
of Surgery,
Massachusetts General Hospital and Harvard Boston, Massachusetts 02114 Submitted
for publication
The past decade has witnessed an explosion in the number of candidate hormones of the gut [2, 111. We have studied VIP, a recently isolated peptide [17] with known structure [ 191and broad biological activities [l, 10, 15, 18, 241. It has been synthesized [4] and the biological activity of the synthetic material has been found similar to the partially purified natural peptide [4]. The producing cells have also been demonstrated by immunofluorescence [ 161, although this has been the subject of some debate recently [ 141. We have studied the endogenous release of the peptide and found that calcium is a powerful VIP stimulant [6]. This is not surprising since calcium is a known releaser of most gut peptides [6]. We have also found that pentagastrin in pharmacological doses is a powerful releaser of the peptide [7]. This may indicate interhormonal relationships. VIP has received considerable interest recently because of its implication in the WDHA syndrome [3, 201. In that syndrome, the endogenous elevation of VIP is associated with a number of symptoms which are similar to the known biological actions of the peptide. This includes the stimulation of intestinal secretion [l, 13,201, inhibition of gastric acid secretion [3, 15,20, 241, and probably other VIP actions like glycogenolysis [ 12, 231 and vasodilatation [17, 231. This study was undertaken in order to study the release of VIP by intraluminal
MURRAY, B.S., AND Medical
School.
January 27, 1977
osmotic stimulation so as to see whether or not the changes observed with the tumoral endogenous release of the peptide could be reproduced, at lease in part, by what could amount to a physiological stimulus. METHODS
Seven mongrel dogs of both sexes (weight 18-22 kg) were used. Five of the dogs were submitted to a midline laparotomy incision under surital anesthesia. Three hundred milliliters of normal saline were infused in the distal duodenum of three dogs over 1 hr (control). This was followed by 300 ml of 6% hypertonic saline similarly infused over 1 hr. Two weeks later the experiment was repeated, but the hypertonic saline was administered in a concentration of 3%. This was followed in two dogs by transposing a loop of the jejunum with an intact blood supply anterior to the duodenum, anastomosing one end of the loop to the duodenum in end-to-side fashion with the blind and closed end secured subcutaneously. This resulted in a jejunal conduit to the duodenum, with enough extraabdominal projection to allow intraduodenal fluid instillation in the “closed” animal (Fig. 1) with hypertonic saline intraduodenally. This was repeated in one instance with the 6% solution and in the two animals with 3% solution. Blood was drawn from a peripheral vein at 0, 3, 5, 10, 20, 40, and 60 min and plasma was assayed for VIP and insulin. VIP was measured by a sensitive and
25 Copyright All rights
0 1977 by Academic Press. Inc. of reproduction in any form reserved.
ISSN 0022-4804
26
JOURNAL
OF SURGICAL
RESEARCH:
VOL. 23, NO. 1, JULY 1977
FIG. 1. Jejunal conduit to the duodenum. This has been constructed to study the effect of intraluminal osmotic stimulation on the release of VIP in the “closed” animal, as opposed to the “laparotomized” one.
*p
OF SURGICAL
23, 25-30 (1977)
RESEARCH
Release of Vasoactive
Intestinal Peptide Osmotic Stimuli
(VIP) by Intraluminal
AMIN M. EBEID, M.D. ,PETER B. SOETERS, M.D. ,PHILLIP JOSEF E. FISCHER, M.D. Departmeni
of Surgery,
Massachusetts General Hospital and Harvard Boston, Massachusetts 02114 Submitted
for publication
The past decade has witnessed an explosion in the number of candidate hormones of the gut [2, 111. We have studied VIP, a recently isolated peptide [17] with known structure [ 191and broad biological activities [l, 10, 15, 18, 241. It has been synthesized [4] and the biological activity of the synthetic material has been found similar to the partially purified natural peptide [4]. The producing cells have also been demonstrated by immunofluorescence [ 161, although this has been the subject of some debate recently [ 141. We have studied the endogenous release of the peptide and found that calcium is a powerful VIP stimulant [6]. This is not surprising since calcium is a known releaser of most gut peptides [6]. We have also found that pentagastrin in pharmacological doses is a powerful releaser of the peptide [7]. This may indicate interhormonal relationships. VIP has received considerable interest recently because of its implication in the WDHA syndrome [3, 201. In that syndrome, the endogenous elevation of VIP is associated with a number of symptoms which are similar to the known biological actions of the peptide. This includes the stimulation of intestinal secretion [l, 13,201, inhibition of gastric acid secretion [3, 15,20, 241, and probably other VIP actions like glycogenolysis [ 12, 231 and vasodilatation [17, 231. This study was undertaken in order to study the release of VIP by intraluminal
MURRAY, B.S., AND Medical
School.
January 27, 1977
osmotic stimulation so as to see whether or not the changes observed with the tumoral endogenous release of the peptide could be reproduced, at lease in part, by what could amount to a physiological stimulus. METHODS
Seven mongrel dogs of both sexes (weight 18-22 kg) were used. Five of the dogs were submitted to a midline laparotomy incision under surital anesthesia. Three hundred milliliters of normal saline were infused in the distal duodenum of three dogs over 1 hr (control). This was followed by 300 ml of 6% hypertonic saline similarly infused over 1 hr. Two weeks later the experiment was repeated, but the hypertonic saline was administered in a concentration of 3%. This was followed in two dogs by transposing a loop of the jejunum with an intact blood supply anterior to the duodenum, anastomosing one end of the loop to the duodenum in end-to-side fashion with the blind and closed end secured subcutaneously. This resulted in a jejunal conduit to the duodenum, with enough extraabdominal projection to allow intraduodenal fluid instillation in the “closed” animal (Fig. 1) with hypertonic saline intraduodenally. This was repeated in one instance with the 6% solution and in the two animals with 3% solution. Blood was drawn from a peripheral vein at 0, 3, 5, 10, 20, 40, and 60 min and plasma was assayed for VIP and insulin. VIP was measured by a sensitive and
25 Copyright All rights
0 1977 by Academic Press. Inc. of reproduction in any form reserved.
ISSN 0022-4804
26
JOURNAL
OF SURGICAL
RESEARCH:
VOL. 23, NO. 1, JULY 1977
FIG. 1. Jejunal conduit to the duodenum. This has been constructed to study the effect of intraluminal osmotic stimulation on the release of VIP in the “closed” animal, as opposed to the “laparotomized” one.
*p
