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Gastric secretion after pentagastrin and histamine in the basal secreting ferret
GASTRIC HISTAMINE NICOLA
SECRETION IN THE BASSO,
M. .4ND
D.,* CARL
AFTER BASAL
PENTAGASTRIN SECRETING
JAMES J.
EXPERIMENTAL STUDIES on gastric secretion have been made with pouch, chronic fistula, and isolated stomach preparations of many different species. The physiologic characteristics and drug responses of these species frequently differ from those of humans in several respects. One feature, gastric secretion during basal conditions, is present in man but is almost invariably lacking in dogs, a species commonly used in gastric research. Since preliminary work in our laboratory [S] indicated that the ferret, which is a carnivorous animal like the dog and cat, is a basal secretor, the present investigation was designed to test the suitability of the conscious, vagally intact, chronic fistula laboratory ferret as an experimental model for gastric secretory studies. The responses to logarithmic doses of pentagastrin and to a maximal dose of histamine [8] were determined and compared to basal secretion. METHODS A chronic gastric fistula was established in ten adult female laboratory ferrets (Marshall From the Institute of Gastroenterology. Presbyterian-university of Pennsylvania Medical Center, Philadelphia, Pa. 19104. *Present address: IIa Clinica Chirurgia Policlinica Umberto I, Roma, Itaha. The authors are indebted to Ayerst Laboratories, New York, New York for supplies of gastrin-like pentapeptide ( AY-6608), to Linda Grogan and Carol Peters for technical assistance, and to the William II. Rorer Gastroenterology Research Fund for generous support. Submitted for publication July 16, 1969.
I.. PFEIFFER,
A.
ROTH,
AND FERRET M.
D.,
PH.D.,
PH.D.
Research Animals, Inc., North Rose, New York). In each animal a nylon cannula (11 mm length, 4 mm I.D. ) similar to that described by Alphin and Lin [l] was implanted, during sodium pentabarbital anesthesia, near the most dependent portion of the fundus. Gastric secretory tests were begun 2 weeks after surgery. During the tests the individual ferrets were placed in a small cage, and each gastric cannula was connected to a light rubber tubing passing through the bottom of the cage so as to allow complete freedom of movement. Gastric contents were collected for 1 or 2 hours (basal period), after which either gastrin-like pentapeptide (pentagastrin, AY-6608) at 2, 5, 10, or 20 pg./kg., or histamine phosphate (Eli Lilly) at 67.3 pg. histamine base/kg. was injected intraperitoneally. Thereafter, collections were taken at 15-minute intervals for 2 hours. Volume, pH, and titratable acidity (titrated electrometrically to pH 7.4 with 0.1 N NaOH) were determined for each sample. In addition, total protease activity (pepsin plus gastricsin) was spectrophotometrically assayed (Beckman DU-2 spectrophotometer) on OS-ml. samples of filtered gastric juice by the method of Chiang et al. [2], using a 2% bovine hemoglobin substrate. All animals were fasted overnight (water ad Zibitum) prior to experiments and were allowed a recovery period of at least one day between tests. Each test was repeated twice in every animal. 111
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10,
NO.
3,
MARCH
RESULTS
1970
PENTAGASTRIN II?)
0.2~ (5sg/kg
The basal secretion in the chronic fistula ferret was characterized by a consistent acid and pepsin output. Results of the first hour were comparable to those of the second hour (Fig. 1)) although acid output and total protease output were slightly depressed during the second hour. A dose-responserelationship was observed following pentagastrin administration, and the maximal acid output was elicited after administration of the 10 pg./ kg. dose (Fig. 4). The peak acid response occurred at 15 minutes postinjection time with the 2 and 5 pg./kg. dose, and at 30 minutes with the 10 pg./kg. dose (Figs. 2-4). However, increasing the dose to 20 pg./kg. resulted in a submaximal acid secretory response, stim-
BASAL
30
120
90 MIt?tTES
Acid output was moderately increased following 5 kg. of gastrin-like pentapeptide/kg. Each point representsthe mean + SE of 20 tests.
Fig. 3.
PENTAGASTRIN (lOwg/kgI.f?)
0.5-1 T -4 Sa 0.4-
.
‘lT 4J
0.2
bT\T 0.1 O’-
l I
1I BASAL
30
60 MINUTES
90
120
4. Acid output was greatly stimulated by a single, 10 pg./kg. dose of gastrin-like pentapeptide and remained elevated after 2 hours. Each point representsthe mean -t- SE of 20 tests. Fig.
1st hr. 2nd hr.
1st hr. 2nd
hr.
1. Acid output (left) and protease output (right) in the chronic fistula ferret during basal conditions. Each bar represents the mean value +- SE of 20 experiments. Note the high level of basal secretion during fasting conditions. Fig.
ulating about one-half the acid output as the 10 pg./ kg. dose (Fig. 5). The pattern of the protease secretory rePENTAGASTRIN (20 &kg IF) o.31
o.2
PENTAGASTRIN
01 :’ I , , , , , , ,
f-*--r 4
,
BASAL
,
,
30
,
,
60
(
,
90
1
120
Acid secretory responseto a single IP dose of gastrin-like pentapeptide. This low dose (2 vg./‘kg.) induced only a slight stimulation. Each point representsthe mean f SE of 20 tests. 112
2.
BASAL
I
MINUTES
Fig.
I
30
60 MINUTES
90
120
5. The highest dose of gastrin-like pentapeptide (20 reg./kg.) stimulated acid output greatly, but lessthan the maximal dose (10 pg./ kg.) tested. Each point representsthe mean + SE of 20 tests. Fig.
BASSO
sponse following pentagastrin stimulation differed from the acid response; a maximal output was stimulated by the lowest dose (2 pg./kg.) of pentagastrin (Fig. 6). The 10 pg./ kg, dose of pentagastrin, which had elicited the maximal acid response, induced a ‘washing out” effect on total protease concentration
ET
AL.:
GASTRIC
SECRETION
after stimulation (Fig. 7). The histamine stimulation with 67.3 pg./kg. IP, previously shown to be a maximal dose [8], induced pepsin (Fig. 8) and acid (Fig. 9) responses which were lower than those induced with the 10 pg./kg. dose of pentagastrin. The correlation of the maximal acid output with the basal acid output, for each animal, is illustrated in Fig. 10, following maximal histamine and pentagastrin stimulation. A linear relationship was found between the basal secretion and the histamine response (correlation coefficient; 0.662, p < 0.05) and the pencoefficient; tagastrin response (correlation 0.762, p < 0.05). The slopes of the regression -----HISTAMINE PENTAGASTRIN
6. In contrast to the maximal, acid secretory dose ( 10 pg./kg.) of pentagastrin, a lower dose (2 pg./kg.) elicited the maximal protease (pepsin + gastricsin) output in the chronic fistula ferret. Each bar represents the mean + SE of 20 tests.
67.3
yg/kg IOpg/kg
II? I.P.
Fig.
----
HISTAMINE PENTAGASTRIN
623pg/kg lOpg/kg
4BASAL
30 60 MINUTES
90
8. Total protease output was briefly increasedfollowing dosesof pentagastrin (10 pg./ kg.) and histamine (67.3 Fg./kg.) which were maximally stimulatory for acid output. Each point representsthe mean +- SE of 20 tests. Fig.
II? I.!?
I
-E
HISTAMINE o.3~ 613yg/kg
7. The concentration of protease in the gastric contents following maximal histamine (67.3 pg./kg.) or pentagastrin ( 10 wg./kg. 1 stimulation was decreaseddue to a “washing-out” effect of the increased volume output. These doses were maximally stimulatory with respect to acid output. Each point represents the mean + SE of 20 tests.
1.P
Fig.
9. In contrast to the prolonged stimulation of acid output following maximal pentagastrin stimulation, the responsefollowing maximal histamine stimulation was less and returned to normal limits within 105 minutes. Each point represents the mean f SE of 20 experiments. Fig.
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10,
NO.
3,
MARCH
1970
.i 200. x \ w” 150. =i ; 2 -I 4 3
100.
50.
200
400
600 MAX.
800 OUTPUT
1,000 ,uEq/30
1,200 min
I.400
Fig. 10. The maximal acid output following pentagastrin or histamine stimulation in individual chronic fistula ferrets was closely correlated with the basal output of acid. Correlation coefficients of 0.662 and 0.762 were calculated for histamine, and pentagastrin, respectively.
lines for parallel.
the two
agents were essentially
DISCUSSION Although the ferret has been used for many years for veterinary research, this species has only recently been introduced for investigations of the gastrointestinal tract, previous studies relating primarily to gastric ultrastructure [7, 9, lo] or the influence of histamine on gastric secretion [8]. It is apparent that the chronic fistula ferret provides a good model for study of gastric physiology, since this species tolerates surgery well (chronic fistula ferrets having been kept for over 1% years), has a stomach anatomically similar to man, and has a consistent basal secretion. Although man is a basal secretor, most experimental animals do not have this characteristic except the rat, which is relatively resistant to histamine and has a specialized gastric structure. Because of its consistent basal secretion, it is possible in the ferret to compare the pentagastrin and histamine responses to a basal gastric secretion. The
linear
relationship
found
in
correlating
these parameters in this study suggeststhat an individualized secretory capacity exists in individual animals of this species. Lee and Thompson [6] have recently shown that the chronic fistula rat is relatively insensitive to pentagastrin, requiring 400 pg./kg. SC to produce a peak response. The maximal dose for the ferret (10 pg./kg. IP) corresponds closely, however, to doses required for peak 114
outputs in the chronic fistula dog [ 111, and for optimal responses following single subcutaneous dosesof pentagastrin in man [ 131. Other investigators [5, 121 have illustrated the stimulatory effect of pentagastrin on pepsin secretion in man, and the maximal secretory response pattern observed here in the chronic fistula ferret is similar to the pattern described by Wormsley et al. [12] for man. The mechanism of the depressed gastric acid output following a supramaximal dose in the chronic fistula ferret is not known. It differs from the observation of transitory inhibition previously reported in this species following supramaximal histamine stimulation [8] since the latter “toxic” effect occurred only in the early part of the dose-response curve. Similarly, it does not appear to correspond to the acid inhibition observed by Emas and Grossman [3] in the dog (but not in the cat) with supramaximal dosesof pentagastrin, since this observation appeared to relate to water and/or electrolyte depletion during continuous drug infusion. Possibly the supramaximal inhibition observed in the present experiments were induced by the same (unidentified) mechanism in which gastric acid secretion was inhibited in the Heidenhain pouch dog following a single, supramaximal intravenous dose of gastrin extract, as reported by Gillespie and Grossman [ 41. SUMMARY Gastric
secretory
experiments
were
con-
ducted with pentagastrin and histamine on the
BASSO
chronic fistula ferret in order to evaluate the physiologic similarity of this preparation to man. Results indicated that the experimental model is suitable for gastric studies, and that the conscious ferret has a consistent basal secretion, uniquely similar to man. In addition, the ferret is highly sensitive to pentagastrin, like man and the cat and dog. Peak acid output in the chronic fistula ferret was observed following a single intraperitoneal dose of 10 pg. pentagastrin/kg. Protease output was also significantly increased following 2 pg. pentagastrin/kg. The secretory outputs following maximal pentagastrin stimulation in this preparation exceeded the maximal outputs following maximal histamine stimulation, although histamine was also a potent stimulant. Due to the consistent basal secretion observed in this species, it was possible to compare maximal stimulated responses to basal secretion in individual animals. The maximal response of individual animals correlated well with the level of basal secretion of acid. Because of the foregoing characteristics, and because of the gastric anatomic similarity to man and surgical tolerance, the ferret appears to be a suitable model for studies of gastric physiology.
3.
4.
5.
6.
7.
8.
9.
11.
REFERENCES 12. 1.
2.
Alphin, chronic
R. S., and denervated
Lin, T. H. Preparation of gastric pouches in the rat. Amer. J. Physiol. 197:257, 1959. Chiang, L., Sanchez-Chiang, L., Wolf, S., and Tang, J. The separate determination of human
13.
AL.:
GASTRIC
SECRETIOS
pepsin and gastricsin. Proc. Sot. Exp. Biol. Med. 122:700, 1966. Emas, S., and Grossman, M. I. Comparison of gastric secretion in conscious dogs and cats. Gastroenterology 42:29, 1967. Gillespie, I. E., and Grossman, M. I. Inhibition of gastric secretion by extracts containing gastrin. Gastroenterology 44:301, 1963. Koster, K. H., Faber, V., and Rodbro, P. Comparative effects of tetragastrin and histamine on pepsin secretion in man. Scud. J. Gastroenterol. 3:106, 1968. Lee, Y. H., and Thompson, J, H. Response of rats with chronic gastric fistulas to subcutaneous injections of histamine, ICI-50123, and insulin. Amer. J. Dig. Dis. 14:14, 1969. Pfeiffer, C. J., and Stephens, R. J. Ultrastructural changes of the parietal cell in the ferret gastric mwosa induced by pylorus ligation and glucocorticoid administration. J. Ultrustruct. Re.r. 21:524, 1968. Pfeiffer, C. J., and Peters, C. M. Gastric secretion in the chronic fistula ferret. Gastroenterology 57:518, 1969. Pfeiffer, C. J., and Weibel, J. The antral clear cell-a new cell type discovered in the pyloricantral mucosa of the ferret. J. Ultrastruct. Res.
29:550, 10.
ET
1969.
Stephens, R. J., and Pfeiffer, C. J. Ultrastructure of the gastric mucosa of normal laboratory ferrets. I. Ultrastruct. Res. 22:45, 1968. Venables, C. W., Rudick, J., Kark, A. E., and Dreiling, D. A. Effects of commercial pancreozymin preparation (Cecekin) and gastrin pentapeptide upon acid and pepsin secretion in gastric fistula dogs. J. Surg. Res. 9:55, 1969. Wormsley, K. G., Mahoney, M. P., and Ng, XI. Effects of a gastrin-like pentapeptide, ICI 50123. Lancet 1:993, 1966. Wormsley, K. G., Mahoney, M. P., and Kay, G. Gastric response to subcutaneous injection of a gastrin-like pentapeptide. Gwt 8:475:1967.
SECRETION IN THE BASSO,
M. .4ND
D.,* CARL
AFTER BASAL
PENTAGASTRIN SECRETING
JAMES J.
EXPERIMENTAL STUDIES on gastric secretion have been made with pouch, chronic fistula, and isolated stomach preparations of many different species. The physiologic characteristics and drug responses of these species frequently differ from those of humans in several respects. One feature, gastric secretion during basal conditions, is present in man but is almost invariably lacking in dogs, a species commonly used in gastric research. Since preliminary work in our laboratory [S] indicated that the ferret, which is a carnivorous animal like the dog and cat, is a basal secretor, the present investigation was designed to test the suitability of the conscious, vagally intact, chronic fistula laboratory ferret as an experimental model for gastric secretory studies. The responses to logarithmic doses of pentagastrin and to a maximal dose of histamine [8] were determined and compared to basal secretion. METHODS A chronic gastric fistula was established in ten adult female laboratory ferrets (Marshall From the Institute of Gastroenterology. Presbyterian-university of Pennsylvania Medical Center, Philadelphia, Pa. 19104. *Present address: IIa Clinica Chirurgia Policlinica Umberto I, Roma, Itaha. The authors are indebted to Ayerst Laboratories, New York, New York for supplies of gastrin-like pentapeptide ( AY-6608), to Linda Grogan and Carol Peters for technical assistance, and to the William II. Rorer Gastroenterology Research Fund for generous support. Submitted for publication July 16, 1969.
I.. PFEIFFER,
A.
ROTH,
AND FERRET M.
D.,
PH.D.,
PH.D.
Research Animals, Inc., North Rose, New York). In each animal a nylon cannula (11 mm length, 4 mm I.D. ) similar to that described by Alphin and Lin [l] was implanted, during sodium pentabarbital anesthesia, near the most dependent portion of the fundus. Gastric secretory tests were begun 2 weeks after surgery. During the tests the individual ferrets were placed in a small cage, and each gastric cannula was connected to a light rubber tubing passing through the bottom of the cage so as to allow complete freedom of movement. Gastric contents were collected for 1 or 2 hours (basal period), after which either gastrin-like pentapeptide (pentagastrin, AY-6608) at 2, 5, 10, or 20 pg./kg., or histamine phosphate (Eli Lilly) at 67.3 pg. histamine base/kg. was injected intraperitoneally. Thereafter, collections were taken at 15-minute intervals for 2 hours. Volume, pH, and titratable acidity (titrated electrometrically to pH 7.4 with 0.1 N NaOH) were determined for each sample. In addition, total protease activity (pepsin plus gastricsin) was spectrophotometrically assayed (Beckman DU-2 spectrophotometer) on OS-ml. samples of filtered gastric juice by the method of Chiang et al. [2], using a 2% bovine hemoglobin substrate. All animals were fasted overnight (water ad Zibitum) prior to experiments and were allowed a recovery period of at least one day between tests. Each test was repeated twice in every animal. 111
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10,
NO.
3,
MARCH
RESULTS
1970
PENTAGASTRIN II?)
0.2~ (5sg/kg
The basal secretion in the chronic fistula ferret was characterized by a consistent acid and pepsin output. Results of the first hour were comparable to those of the second hour (Fig. 1)) although acid output and total protease output were slightly depressed during the second hour. A dose-responserelationship was observed following pentagastrin administration, and the maximal acid output was elicited after administration of the 10 pg./ kg. dose (Fig. 4). The peak acid response occurred at 15 minutes postinjection time with the 2 and 5 pg./kg. dose, and at 30 minutes with the 10 pg./kg. dose (Figs. 2-4). However, increasing the dose to 20 pg./kg. resulted in a submaximal acid secretory response, stim-
BASAL
30
120
90 MIt?tTES
Acid output was moderately increased following 5 kg. of gastrin-like pentapeptide/kg. Each point representsthe mean + SE of 20 tests.
Fig. 3.
PENTAGASTRIN (lOwg/kgI.f?)
0.5-1 T -4 Sa 0.4-
.
‘lT 4J
0.2
bT\T 0.1 O’-
l I
1I BASAL
30
60 MINUTES
90
120
4. Acid output was greatly stimulated by a single, 10 pg./kg. dose of gastrin-like pentapeptide and remained elevated after 2 hours. Each point representsthe mean -t- SE of 20 tests. Fig.
1st hr. 2nd hr.
1st hr. 2nd
hr.
1. Acid output (left) and protease output (right) in the chronic fistula ferret during basal conditions. Each bar represents the mean value +- SE of 20 experiments. Note the high level of basal secretion during fasting conditions. Fig.
ulating about one-half the acid output as the 10 pg./ kg. dose (Fig. 5). The pattern of the protease secretory rePENTAGASTRIN (20 &kg IF) o.31
o.2
PENTAGASTRIN
01 :’ I , , , , , , ,
f-*--r 4
,
BASAL
,
,
30
,
,
60
(
,
90
1
120
Acid secretory responseto a single IP dose of gastrin-like pentapeptide. This low dose (2 vg./‘kg.) induced only a slight stimulation. Each point representsthe mean f SE of 20 tests. 112
2.
BASAL
I
MINUTES
Fig.
I
30
60 MINUTES
90
120
5. The highest dose of gastrin-like pentapeptide (20 reg./kg.) stimulated acid output greatly, but lessthan the maximal dose (10 pg./ kg.) tested. Each point representsthe mean + SE of 20 tests. Fig.
BASSO
sponse following pentagastrin stimulation differed from the acid response; a maximal output was stimulated by the lowest dose (2 pg./kg.) of pentagastrin (Fig. 6). The 10 pg./ kg, dose of pentagastrin, which had elicited the maximal acid response, induced a ‘washing out” effect on total protease concentration
ET
AL.:
GASTRIC
SECRETION
after stimulation (Fig. 7). The histamine stimulation with 67.3 pg./kg. IP, previously shown to be a maximal dose [8], induced pepsin (Fig. 8) and acid (Fig. 9) responses which were lower than those induced with the 10 pg./kg. dose of pentagastrin. The correlation of the maximal acid output with the basal acid output, for each animal, is illustrated in Fig. 10, following maximal histamine and pentagastrin stimulation. A linear relationship was found between the basal secretion and the histamine response (correlation coefficient; 0.662, p < 0.05) and the pencoefficient; tagastrin response (correlation 0.762, p < 0.05). The slopes of the regression -----HISTAMINE PENTAGASTRIN
6. In contrast to the maximal, acid secretory dose ( 10 pg./kg.) of pentagastrin, a lower dose (2 pg./kg.) elicited the maximal protease (pepsin + gastricsin) output in the chronic fistula ferret. Each bar represents the mean + SE of 20 tests.
67.3
yg/kg IOpg/kg
II? I.P.
Fig.
----
HISTAMINE PENTAGASTRIN
623pg/kg lOpg/kg
4BASAL
30 60 MINUTES
90
8. Total protease output was briefly increasedfollowing dosesof pentagastrin (10 pg./ kg.) and histamine (67.3 Fg./kg.) which were maximally stimulatory for acid output. Each point representsthe mean +- SE of 20 tests. Fig.
II? I.!?
I
-E
HISTAMINE o.3~ 613yg/kg
7. The concentration of protease in the gastric contents following maximal histamine (67.3 pg./kg.) or pentagastrin ( 10 wg./kg. 1 stimulation was decreaseddue to a “washing-out” effect of the increased volume output. These doses were maximally stimulatory with respect to acid output. Each point represents the mean + SE of 20 tests.
1.P
Fig.
9. In contrast to the prolonged stimulation of acid output following maximal pentagastrin stimulation, the responsefollowing maximal histamine stimulation was less and returned to normal limits within 105 minutes. Each point represents the mean f SE of 20 experiments. Fig.
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10,
NO.
3,
MARCH
1970
.i 200. x \ w” 150. =i ; 2 -I 4 3
100.
50.
200
400
600 MAX.
800 OUTPUT
1,000 ,uEq/30
1,200 min
I.400
Fig. 10. The maximal acid output following pentagastrin or histamine stimulation in individual chronic fistula ferrets was closely correlated with the basal output of acid. Correlation coefficients of 0.662 and 0.762 were calculated for histamine, and pentagastrin, respectively.
lines for parallel.
the two
agents were essentially
DISCUSSION Although the ferret has been used for many years for veterinary research, this species has only recently been introduced for investigations of the gastrointestinal tract, previous studies relating primarily to gastric ultrastructure [7, 9, lo] or the influence of histamine on gastric secretion [8]. It is apparent that the chronic fistula ferret provides a good model for study of gastric physiology, since this species tolerates surgery well (chronic fistula ferrets having been kept for over 1% years), has a stomach anatomically similar to man, and has a consistent basal secretion. Although man is a basal secretor, most experimental animals do not have this characteristic except the rat, which is relatively resistant to histamine and has a specialized gastric structure. Because of its consistent basal secretion, it is possible in the ferret to compare the pentagastrin and histamine responses to a basal gastric secretion. The
linear
relationship
found
in
correlating
these parameters in this study suggeststhat an individualized secretory capacity exists in individual animals of this species. Lee and Thompson [6] have recently shown that the chronic fistula rat is relatively insensitive to pentagastrin, requiring 400 pg./kg. SC to produce a peak response. The maximal dose for the ferret (10 pg./kg. IP) corresponds closely, however, to doses required for peak 114
outputs in the chronic fistula dog [ 111, and for optimal responses following single subcutaneous dosesof pentagastrin in man [ 131. Other investigators [5, 121 have illustrated the stimulatory effect of pentagastrin on pepsin secretion in man, and the maximal secretory response pattern observed here in the chronic fistula ferret is similar to the pattern described by Wormsley et al. [12] for man. The mechanism of the depressed gastric acid output following a supramaximal dose in the chronic fistula ferret is not known. It differs from the observation of transitory inhibition previously reported in this species following supramaximal histamine stimulation [8] since the latter “toxic” effect occurred only in the early part of the dose-response curve. Similarly, it does not appear to correspond to the acid inhibition observed by Emas and Grossman [3] in the dog (but not in the cat) with supramaximal dosesof pentagastrin, since this observation appeared to relate to water and/or electrolyte depletion during continuous drug infusion. Possibly the supramaximal inhibition observed in the present experiments were induced by the same (unidentified) mechanism in which gastric acid secretion was inhibited in the Heidenhain pouch dog following a single, supramaximal intravenous dose of gastrin extract, as reported by Gillespie and Grossman [ 41. SUMMARY Gastric
secretory
experiments
were
con-
ducted with pentagastrin and histamine on the
BASSO
chronic fistula ferret in order to evaluate the physiologic similarity of this preparation to man. Results indicated that the experimental model is suitable for gastric studies, and that the conscious ferret has a consistent basal secretion, uniquely similar to man. In addition, the ferret is highly sensitive to pentagastrin, like man and the cat and dog. Peak acid output in the chronic fistula ferret was observed following a single intraperitoneal dose of 10 pg. pentagastrin/kg. Protease output was also significantly increased following 2 pg. pentagastrin/kg. The secretory outputs following maximal pentagastrin stimulation in this preparation exceeded the maximal outputs following maximal histamine stimulation, although histamine was also a potent stimulant. Due to the consistent basal secretion observed in this species, it was possible to compare maximal stimulated responses to basal secretion in individual animals. The maximal response of individual animals correlated well with the level of basal secretion of acid. Because of the foregoing characteristics, and because of the gastric anatomic similarity to man and surgical tolerance, the ferret appears to be a suitable model for studies of gastric physiology.
3.
4.
5.
6.
7.
8.
9.
11.
REFERENCES 12. 1.
2.
Alphin, chronic
R. S., and denervated
Lin, T. H. Preparation of gastric pouches in the rat. Amer. J. Physiol. 197:257, 1959. Chiang, L., Sanchez-Chiang, L., Wolf, S., and Tang, J. The separate determination of human
13.
AL.:
GASTRIC
SECRETIOS
pepsin and gastricsin. Proc. Sot. Exp. Biol. Med. 122:700, 1966. Emas, S., and Grossman, M. I. Comparison of gastric secretion in conscious dogs and cats. Gastroenterology 42:29, 1967. Gillespie, I. E., and Grossman, M. I. Inhibition of gastric secretion by extracts containing gastrin. Gastroenterology 44:301, 1963. Koster, K. H., Faber, V., and Rodbro, P. Comparative effects of tetragastrin and histamine on pepsin secretion in man. Scud. J. Gastroenterol. 3:106, 1968. Lee, Y. H., and Thompson, J, H. Response of rats with chronic gastric fistulas to subcutaneous injections of histamine, ICI-50123, and insulin. Amer. J. Dig. Dis. 14:14, 1969. Pfeiffer, C. J., and Stephens, R. J. Ultrastructural changes of the parietal cell in the ferret gastric mwosa induced by pylorus ligation and glucocorticoid administration. J. Ultrustruct. Re.r. 21:524, 1968. Pfeiffer, C. J., and Peters, C. M. Gastric secretion in the chronic fistula ferret. Gastroenterology 57:518, 1969. Pfeiffer, C. J., and Weibel, J. The antral clear cell-a new cell type discovered in the pyloricantral mucosa of the ferret. J. Ultrastruct. Res.
29:550, 10.
ET
1969.
Stephens, R. J., and Pfeiffer, C. J. Ultrastructure of the gastric mucosa of normal laboratory ferrets. I. Ultrastruct. Res. 22:45, 1968. Venables, C. W., Rudick, J., Kark, A. E., and Dreiling, D. A. Effects of commercial pancreozymin preparation (Cecekin) and gastrin pentapeptide upon acid and pepsin secretion in gastric fistula dogs. J. Surg. Res. 9:55, 1969. Wormsley, K. G., Mahoney, M. P., and Ng, XI. Effects of a gastrin-like pentapeptide, ICI 50123. Lancet 1:993, 1966. Wormsley, K. G., Mahoney, M. P., and Kay, G. Gastric response to subcutaneous injection of a gastrin-like pentapeptide. Gwt 8:475:1967.