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1.
Summary Ion-sensitive glass microelectrodes, conventional microelectrodes and isotope flux measurements were employed inNecturus gallbladder epithelium to study intracellular sodium activity, [Na]
i
, electrical parameters of epithelial cells, and properties of active sodium transport. Mean control values were: [Na]
i
: 9.2 to 12.1mm; transepithelial potential difference,
ms
: –1.5 mV (lumen negative); basolateral cell membrane potential,
es
: –62 mV (cell interior negative); sodium conductance of the luminal cell membrane,g
Na: 12 mho cm–2; active transcellular sodium flux, 88 to 101 pmol cm–2 sec–1 (estimated as instantaneous short-circuit current). Replacement of luminal Na by K led to a decrease of the intracellular sodium activity at a rate commensurate to the rate of active sodium extrusion across the basolateral cell membrane. Mucosal application of amphotericin B resulted in an increase of the luminal membrane conductance, a rise of intracellular sodium activity, and an increase of short-circuit current and unidirectional mucosa to serosa sodium flux. Conclusions: (i) sodium transport across the basolateral membrane can proceed against a steeper chemical potential difference at a higher rate than encountered under control conditions; (ii) the luminal Na-conductance is too low to accommodate sodium influx at the rate of active basolateral sodium extrusion, suggesting involvement of an electrically silent luminal transport mechanism; (iii) sodium entry across the luminal membrane is the rate-limiting step of transcellular sodium transport and active sodium extrusion across the basolateral cell membrane is not saturated under control conditions. 相似文献
2.
Summary To determine if harmala alkaloids affect transport systems other than (Na +K)-ATPase, effects of harmaline on Na and water fluxes were studied in amphibian skins. Net Na flux was evaluated from short-circuit current, and water flux monitored with automatic, volumetric methods. At 2 to 5mm, harmaline consistently inhibited SCC and prevented the natriferic effects of oxytocin and norepinephrine. However, at 0.1 to 0.5mm, harmaline produced an increase in SCC inhibitable with amiloride. The stimulatory effects of harmaline and oxytocin were either nonadditive or additive depending on whether the hallucinogen was present in the inner solution or in the outer solution bathing the skin, respectively. Water flow was not modified by harmaline on the outer medium. In contrast, addition of the drug to the inner medium elicited a conspicuous, sustained, vasopressin-like, hydrosmotic effect, comparable to and competitive with those of vasopressin and norepinephrine. The ensemble of these results suggests that harmaline may affect three distinct transport systems: (i) the Na pump; (ii) the cyclic nucleotide system; (iii) the Na entry pathway at the outer membrane of the skin that is also activated by agents such as diphenylhydantoin, lanthanides and propranolol. 相似文献
3.
L. C. Isaacson 《The Journal of membrane biology》1976,26(1):301-317
Summary In amphibian epithelia, amiloride reduces net sodium transport by hindering the entry of sodium to the active transport mechanism, that is, by increasing the series resistance (R
ser
). Theoretically, therefore, analysis of amiloride-induced changes in potential differences and short-circuit current should yield numerical estimates of all the parameters in the equivalent electrical circuit of the sodium transport mechanism.The concept has been explored by analysis of such changes in toad skins (Xenopus laevis) bathed in hypotonic sulphate Ringer's, after exposure to varying doses of amiloride, or to amphotericin, dinitrophenol or Pitressin.The estimated values ofR
ser
, of the electromotive force of the sodium pump (E
Na), and of the shunt resistance (R
sh
) were independent of the dose of amiloride employed. Skins bathed in hypotonic sulphate Ringer's exhibited a progressive rise inE
Na. Amphotericin produced a fall inR
ser
, while dinitrophenol caused a fall inE
Na; washout of the drugs reversed these effects. Pitressin produced a fall in bothR
ser
andR
sh
, with a rise inE
Na. These results are in accord with earlier suggestions regarding the site(s) of action of these agents. 相似文献
4.
Summary The influence of adrenal steroids on sodium transport in hen coprodeum was investigated by electrophysiological methods. Laying hens were maintained on low-NaCl diet (LS), or on high-NaCl diet (HS). HS hens were pretreated with aldosterone (128 g/kg) or dexamethasone (1 mg/kg) before experiment. A group of LS hens received spironolactone (70 or 160 mg/kg, for three days). The effects of these dietary and hormonal manipulations on the amiloride-sensitive part of the short-circuit current were examined. This part is in excellent agreement with the net Na flux, and therefore a direct electrical measurement for Na transport. After depolarizing the basolateral membrane potential with a high K concentration, the apical Na permeability and the intracellular Na activity were investigated by currentvoltage relations for the different experimental conditions.Plasma aldosterone concentrations (PA) were low in HS hens, dexamethasone-treated HS hens and spironolactonetreated LS hens (<70pm). In contrast LS hens and aldosteronetreated HS hens had a PA concentration of 596±70 and 583±172pm, respectively. LS diet (chronic stimulation) had the largest stimulatory effect on Na transport and apical Na permeability. Hormone-treated animals had three- to fourfold lower values. Spironolactone supply in LS hens decreased Na transport and apical Na permeability about 50%.The results provide evidence that both mineralo- and glucocorticoids stimulate Na transport in this tissue by increasing the apical Na permeability. Quantitative differences between acute and chronic stimulation reveal a secondary slower adaptation in apical membrane properties. 相似文献
5.
R Dimaline 《Peptides》1983,4(4):457-462
The amphibian skin decapeptide caerulein is structurally related to the mammalian peptides gastrin and CCK, suggesting that the peptides might share a common evolutionary history. It has been suggested that caerulein is the amphibian counterpart of gastrin and CCK, and that the Amphibia do not possess authentic gastric and CCK. High Performance Liquid Chromatography (HPLC) in conjunction with radioimmunoassay using a caerulein-specific antiserum and C-terminal CCK antisera, was used to characterize CCK-and caerulein-like peptides in amphibian brain and gut. In the brain of Xenopus laevis, two CCK-like peptides were present, one of which was indistinguishable by HPLC from mammalian CCK8. No decapeptide caerulein was detected in the brain of Xenopus laevis or Rana temporaria. In the stomach of Xenopus and in the intestine of both species studied, CCK-like and caerulein-like peptides were present. The results indicate therefore that the Amphibia possess CCK8-like rather than caerulein-like peptides in brain. In contrast, stomach and intestine contain both CCK-like and caerulein-like peptides, but the latter are however distinguishable from the decapeptide found in skin. 相似文献
6.
Action of gastrointestinal hormones on the myoelectric activity of the sphincter of Oddi in living rabbit 总被引:1,自引:0,他引:1
J C Sarles P Delecourt H Castello L Gaeta M Nacchiero J P Amoros M A Devaux R Awad 《Regulatory peptides》1981,2(2):113-124
The aim of this work was to compare the action of gastrointestinal (GI) hormones on the myoelectrical activity of the sphincter of Oddi. Using an experimental design previously described, we studied the electrical activity of the sphincter of Oddi and compared the percentage variation in the number of spikes before and after injection of hormones. Increasing doses of the following hormones were injected i.v. at random: CCK, OP-CCK, caerulein, bombesin, gastrin, secretin and glucagon. CCK and caerulein (as previously found), and also bombesin, OP-CCK and gastrin increased the spikes activity of the sphincter of Oddi. Secretin had no effect and glucagon decreased this activity. There was no tachyphylaxis, but a good dose-effect relationship for each hormone. Compared on a molar basis caerulein is 8 times more effective than CCK and OP-CCK which in turn are more potent than bombesin. Gastrin acts only at pharmacological doses. 相似文献
7.
ABSTRACT The effects of six injections of a range of doses (100–1000 μg/kg bodyweight) of pentagrastrin and single injection of a range of doses of porcine gastrin (10–40 μg/kg bodyweight) and pancreatic glucagon (25–100 μg/kg bodyweight) on cell proliferation in the intestine of fasted rats has been investigated. the end-point employed included the measurement of 14C leucine incorporation and thymidine-derived tritium content of the body of the stomach, duodenum, jejunum, ileum and colon. the carbon 14 and tritium content per μg of tissue in triplicate samples of fifty individually dissected crypts of glands were determined. From these data and the wet weight of the washed, blotted, intestinal segments, values for crypts/μg tissue and crypts/segment were calculated. the results demonstrated that pentagastrin at physiological doses decreased cell proliferation slightly in stomach, while gastrin and glucagon were without effect. In the small intestine, pentagastrin and gastrin were without significant effect with the exception that they increased the weight of the duodenum. In contrast, a high physiological dose of glucagon increased DNA and protein synthesis throughout the small bowel, but particularly in the ileum. Pharmacological doses of pentagastrin and all doses of gastrin appeared to increase cell proliferation in the colon although the possibility could not be excluded that this was due to stimulation of precursor uptake. Gastrin also increased colonic weight. Glucagon had no effects in the colon. These observations are compatible with the hypothesis that (i) the primary effects of gastrin and pentagastrin on the proximal intestine are as secretogogues and effects on cell proliferation may be secondary, (ii) gastrin and pentagastrin at physiological levels do not stimulate small intestinal cell proliferation, however glucagon does, and (iii) gastrin at physiological levels and pentagastrin at pharmacological levels may stimulate cell proliferation in the colon. 相似文献
8.
Yoshitaka Saito Keiichi Itoi Keisuke Horiuchi Tadao Watanabe 《The Journal of membrane biology》1980,53(2):85-93
Summary The effects of furosemide on the chloride-dependent short-circuit current across the toad ciliary epithelium were examined. Under control conditions, the short-circuit current obeyed Michaelis-Menten kinetics against medium chloride concentration, the Michaelis constant (K
m
) for chloride being 90mm and the maximal short-circuit current (V
max) 128 A/cm2. Furosemide added to the aqueous side of the epithelium rapidly reduced the short-circuit current; the effect was reversible. The effect of furosemide addition to the stromal side was much smaller and slower than that from the aqueous side. The dose-dependent range of furosemide action was from 0.1 m to 1mm with 50% inhibition occurring at about 3 m. Line-weaver-Burk plot of the short-circuit current against the chloride concentration showed that furosemide decreased the value ofV
max and increased theK
m
; the inhibition being of mixed type. A Hill plot of the dose-response curve yielding a slope of unity suggested one furosemide molecule combines with one chloride transport site. Probenecid, a competitive inhibitor of organic acid transport, reduced the effects of furosemide significantly when added simultaneously. The involvement of organic acid transport system in the mechanism of furosemide action on chloride transport was suggested.Department of Ophthalmology. 相似文献
9.
G A Gerencser S Y Loo K M Cornette 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1984,176(3):257-260
Both ethanol and silver ions have been shown to affect ion transport across various epithelia. This investigation was principally undertaken to further define mechanisms of silver ions and ethanol, and their possible interactions, on sodium transport across toad skin. Isolated toad skin, mounted between identical oxygenated amphibian bicarbonate Ringer solutions, maintained stable transepithelial potential differences (serosa positive) and short-circuit currents for several hours at 25 degrees C. It was observed that (1) ethanol inhibited the active transcellular component of sodium absorption and this effect was reversible; (2) inhibition of sodium transport by ethanol was directly proportional to the applied concentration; (3) pretreatment with silver ions prevented any ethanol effects; and (4) pretreatment with ethanol prevented any silver ion effects. It was concluded from these results that ethanol induced its inhibitory effects on membrane phospholipids thereby perturbing the function of a sulfhydryl ligand, while silver ion or silver chloride complex binding to this ligand would maintain its function in sodium transport despite the presence of ethanol. 相似文献
10.
A specific receptor for gastrin I has been demonstrated in the rat stomach fundus.Specific binding of 125I-labelled gastrin I was localised to particles sedimenting between 250–20 000 × g. Saturation of binding sites occurred with a gastrin concentration of 10?11 M in an assay system containing 0.6–1.7 mg/ml of homogenate protein. Gastrin binding was shown to be reversible, temperature- and pH-dependent, and susceptible to tryptic digestion. Electron microscopic and enzymatic studies showed the binding fraction to contain predominantly mitochondria. Preincubation of the homogenate with 10?8 M cholecystokinin or secretin inhibited gastrin binding to a greater extent than an equimolar concentration of pentagastrin. Cimetidine, a histamine receptor antagonist, did not affect binding of gastrin to the receptor. 相似文献
11.
When amphibian skin was incubated under conditions in which transepithelial sodium transport was abolished, a conductive transepithelial Cl- flux arose when Cl- was removed from one of the compartments. This flux was matched by short-circuit current and it accounted entirely for transepithelial conductance. Cl- influx was larger than efflux; it was linearly related to the magnitude of transepithelial Cl- concentration difference. When applied to the epithelial surface of the tissue, divalent metal cations such as Co2+, and the ethacrynic acid derivative, indacrinone, reduced rapidly and reversibly both transepithelial Cl- (in)flux and short-circuit current. Frog skin proved to be more sensitive to these inhibitors than toad skin. Further characterization of transepithelial Cl- pathway(s) should benefit from the fact that Cl- across amphibian skin can easily be monitored by the short-circuit current method, and from the availability of agents which inhibit this passive flux rapidly and reversibly. 相似文献
12.
Summary Previously we have shown that the inhibition of active transport by amiloride is noncompetitive with sodium inRana catesbeiana skin, suggesting that amiloride acts at a site separate from the sodium entry site (Benos, D.J., Mandel, L.J., Balaban, R.S. 1979,J. Gen Physiol.
73: 307). In the present study, the effects of a number of sulfhydryl, amino, and carboxyl group selective reagents were studied on short-circuit current (I
sc) as well as the efficacy of amiloride in bullfrog skin, to determine those functional ligands which may be involved with either of these processes.Addition of the sulfhydryl reagent PCMBS (1mm) to the outside bathing medium produced biphasic effects, initially reversibly increasingI
sc by an average 56% followed by a slower, irreversible decay to levels below baseline. In contrast, the addition of 0.1mm PCMB always resulted in a rapid, irreversible decrease inI
sc. When a 40,000 mol wt dextran molecule was attached to PCMB, a stable, reversible increase inI
sc was observed. These observations suggest that at least two populations of-SH groups are involved in Na translocation through the entry step. Amiloride was equally effective in inhibitingI
sc before and after treatment with PCMBS both during the stimulatory as well as the inhibitory phase. The sulfhydryl reducing agent DTT, and oxidizing agent DTNB had only minor influence onI
sc
and did not alter the effectiveness of amiloride.Similarly, the amino reagents, SITS and TNBS did not affectI
sc. However, TNBS decreased the ability of amiloride to inhibit Na entry. These results suggest that an amino group may be involved in the interaction of amiloride and its site, without affecting Na entry.The carboxyl reagents EEDQ, TMO, and three separate carbodiimides were without effect onI
sc or amiloride inhibition. Methylene blue (MB), a molecule that interacts with both carboxyl and hydroxylspecific groups, inhibitedI
sc by 20% and decreased amiloride's ability to inhibitI
sc. These effects, however, are likely to occur from the cytoplasmic side as MB appears to enter into the cells.These results support the notion that amiloride and Na interact with the entry protein at different regions on the membrane. 相似文献
13.
Thyrotropin-releasing hormone (TRH) immunoreactivity has been shown previously to be distributed throughout the gastrointestinal tract and the pancreas. This study demonstrated that TRH given intravenously suppresses, in a dose-related manner, sham-feeding induced food intake and inhibits gastric secretion provoked by infusion of pentagastrin or instillation of 10% liver extract into the stomach. TRH also reduces pancreatic response to secretin, caerulein, feeding a meat meal or duodenal acidification. The findings that TRH inhibits gastric and pancreatic secretions induced by exogenous and endogenous stimulants, and that the inhibition by TRH of post-prandial secretion is not accompanied by any change in serum gastrin, indicate that TRH probably acts directly on the exocrine stomach and pancreas. 相似文献
14.
Stanley D. Hillyard Ronald Sera Harvey C. Gonick 《The Journal of membrane biology》1979,46(4):283-294
Summary Cadmium ion (Cd++) was found not to inhibit active sodium transport across the isolated frog skin when added in 10–3
m concentration to the basal-lateral surface. The same Cd++ concentration similarly had no effect on Na+ transport across the isolated epithelial cell layer from the frog skin, although this dose of Cd++ did inhibit Na+ transport across the frog urinary bladder and large intestine. When 10–3
m Cd++ was added to the apical surface of the isolated frog skin or to the isolated epithelial cells from the frog skin, sodium transport was reversibly stimulated, in contrast to the irreversible inhibition noted above. If equimolar cysteine was added with Cd++ to the apical surface of the skin, however, active Na+ transport was irreversibly inhibited. In conjunction with the inhibition produced by equimolar Cd++ and cysteine, isotopic Cd++ permeation into the tissue was three times higher when added with cysteine than in the absence of cysteine. Thus, the effects of Cd++ on epithelial Na+ transport is variable according to the epithelium studied and the presence of potential carrier molecules. 相似文献
15.
Interaction between Na+-dependent transport systems for sugars and amino acids. Evidence against a role for the sodium gradient 总被引:1,自引:0,他引:1
Summary The concept that interaction between sodium-dependent transport systems represents competition for energy inherent in the transmembrane sodium gradient was examined with the use of isolated intestinal epithelial cells. The isolated cells exhibit transport interactions which are more significant in magnitude than those which have been described for intact tissue preparations. Accumulation of 1mm valine is inhibited 60% by 10mm 3-OMG. Conversely, uptake of 1mm 3-OMG is inhibited only 20% by 10mm valine. These data suggest that 3-OMG must discharge the cellular Na+ gradient more effectively than valine, if Na+ gradient dissipation can be taken as a basis for the inhibitory interaction. However, entry of 10mm 3-OMG is significantly slower than the entry of 10mm valine. Even if appropriate corrections are made for passive substrate entry and for differences in Na/substrate entry stoichiometry, it appears that valine should be somewhat more effective than 3-OMG in discharging the Na+ gradient. In light of these facts, it seems unlikely that the mechanistic basis for interaction between sugar and amino acid transport systems can be related to concomitant co-entry of Na+. It is suggested that the interaction results instead from competition for energized intermediates generated at limited rates by basic energy transduction events associated with the cell membrane which serve in support of a variety of active transport systems. 相似文献
16.
U Katz W van Driessche C Scheffey 《Biology of the cell / under the auspices of the European Cell Biology Organization》1985,55(3):245-250
In early studies of salt transport across frog and toad skin, it was assumed that chloride movement is extracellular. However, later studies suggested that chloride movement is largely transcellular. Chloride transport across toad skin is greatly diminished in skins of salt-acclimated toads (Bufo viridis) and was correlated with the number of mitochondria-rich (m.r.) cells in the epithelium. The activated chloride conductance could be recovered upon in vitro incubation with theophylline. It was found that the short-circuit current (Isc) and the chloride conductance (Gcl) in toad skin could be separated experimentally by selective use of synthetic oxytocin (Syntocinon) or theophylline, and by substituting impermeable anions for chloride. With the use of the vibrating probe we demonstrated directly that chloride-dependent peak currents are localized only over m.r. cells, under hyperpolarized (V = -100 mV) conditions. It is concluded that the m.r. cells form the principal site for passive chloride movement across amphibian skin. This cellular pathway is regulated through a cyclic AMP-mediated process. It is suggested that the spatial separation of the sodium and chloride channels is essential to maintain the granulosum cells which are engaged in sodium transport hyperpolarized, and thus providing the driving force for the sodium entry into the cells. 相似文献
17.
Active transport of sodium ions across the isolated abdominal skin of the frog Rana temporaria after application of arginine-vasotocin (AVT) and 1-deamino-arginine-vasotocin (1dAVT) was studied by measurement of the
short-circuit current (SCC). The maximal increase in the SCC values (26 and 19 mk/cm2) was observed after addition of 10 nM AVT or 100 nM 1dAVT, respectively, to the frog skin basal surface. An increase of concentration
of AVT to 100 nM and of 1dAVT to 1 μM terminated the sodium transport in the frog skin. A preliminary addition of an antagonist
of arginine-vasopressin Via-receptors to the Ringer’s solution at the frog skin basal surface led to a rise in the SCC values in response to administration
of ineffective doses of AVT or 1dAVT. V2-receptor antagonists did not affect the frog skin reaction to administration of these doses of AVT of 1dAVT. 相似文献
18.
Karen K. Hirschi Sharon Kenny Jill D. Justice Patsy M. Brannon 《In vitro cellular & developmental biology. Animal》1991,27(8):660-664
Summary We examined the effects of secretin (0 to 200 nM) and caerulein (0 to 100 nM) on rat pancreatic acinar cells cultured 0 to 48 h in serum-free medium. The effects of 100 nM secretin with 1 nM caerulein were also studied because secretin may potentiate the effects of caerulein. Cellular and media (secreted) lipase
and amylase were analyzed as were cellular DNA and protein content. Cellular lipase and amylase activities significantly decreased
(P<0.0001) over time in all treatment groups, whereas media amylase and lipase significantly increased (P<0.0001). Neither secretin nor caerulein affected cellular lipase or media amylase. However, secretin significantly increased
(P<0.04) and caerulein tended to increase (P<0.08) media lipase in a dose-dependent manner. At 12 h, 10 nM secretin maximally increased media lipase (58%), suggesting that cultured acinar cells remain responsive to secretin in vitro.
Caerulein, at all concentrations, significantly decreased (P<0.001) cellular amylase but exhibited a dose-dependent effect only at 24 h when 100 nM caerulein maximally decreased cellular amylase (34%). Secretin (100 nM) did not alter these effects of caerulein. These results support the proposed role of caerulein in the regulation of amylase
but not a direct role of secretin in the regulation of lipase.
This study was supported in part by grant RO1 DK32690 from the National Institutes of Health, Bethesda, MD. 相似文献
19.
Summary The role of Ca2+ in the stimulation by antidiuretic hormone (ADH) of active sodium transport across the isolated epithelium of frog skin was investigated. This has been done by bathing the blood side with Ca2+-free solution containing 0.1mm EGTA. This Ca2+ depletion halved the resistance but had no significant effect on the short-circuit current (SCC). The sensitivity of both cAMP- and SCC-stimulation to ADH was increased 40-fold by Ca2+ depletion. Sensitivity to stimulation by theophylline was only changed a little, while stimulation by exogenous cAMP was completely unaltered. The increase in sensitivity to ADH was dependent on the duration of preincubation in Ca2+-free solution, which indicates that a slowly exchanging Ca2+ pool is involved in the determination of sensitivity to ADH. We suggest this pool is of cellular origin and the increased sensitivity is due to the decrease of a Ca2+ inhibition of the ADH-stimulated adenylate cyclase. But a direct effect of Ca2+ on binding of ADH to the receptor cannot be excluded. Our results are not compatible with the hypothesis that entry of extracellular Ca2+ is an obligatory step in the natriferic action of ADH, although it may be so in the hydroosmotic action of ADH. We also found the maximal response to ADH to be higher after Ca2+ depletion. This is in agreement with the hypothesis of intracellular Ca2+ as a modulator of the sodium permeability of the outward-facing membrane. 相似文献
20.
Evaluation of the effects of pentagastrin, gastrin and pancreatic glucagon on cell proliferation in the rat gastrointestinal tract 总被引:1,自引:0,他引:1
The effects of six injections of a range of doses (100-1000 micrograms/kg bodyweight) of pentagrastrin and single injection of a range of doses of porcine gastrin (10-40 micrograms/kg bodyweight) and pancreatic glucagon (25-100 micrograms/kg bodyweight) on cell proliferation in the intestine of fasted rats has been investigated. The end-point employed included the measurement of 14C leucine incorporation and thymidine-derived tritium content of the body of the stomach, duodenum, jejunum, ileum and colon. The carbon 14 and tritium content per microgram of tissue in triplicate samples of fifty individually dissected crypts of glands were determined. From these data and the wet weight of the washed, blotted, intestinal segments, values for crypts/micrograms tissue and crypts/segment were calculated. The results demonstrated that pentagastrin at physiological doses decreased cell proliferation slightly in stomach, while gastrin and glucagon were without effect. In the small intestine, pentagastrin and gastrin were without significant effect with the exception that they increased the weight of the duodenum. In contrast, a high physiological dose of glucagon increased DNA and protein synthesis throughout the small bowel, but particularly in the ileum. Pharmacological doses of pentagastrin and all doses of gastrin appeared to increase cell proliferation in the colon although the possibility could not be excluded that this was due to stimulation of precursor uptake. Gastrin also increased colonic weight. Glucagon had no effects in the colon. These observations are compatible with the hypothesis that (i) the primary effects of gastrin and pentagastrin on the proximal intestine are as secretogogues and effects on cell proliferation may be secondary, (ii) gastrin and pentagastrin at physiological levels do not stimulate small intestinal cell proliferation, however glucagon does, and (iii) gastrin at physiological levels and pentagastrin at pharmacological levels may stimulate cell proliferation in the colon. 相似文献