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PubMed1993

Identification of biologically active epidermal growth factor precursor in human fluids and secretions.

A biologically active form of the epidermal growth factor (EGF) precursor has been detected in human fluids and secretions. The secreted protein identified in human urine and milk has an apparent molecular mass of 160-170 kilodaltons and exhibits an affinity for the glycosaminoglycan heparin. More importantly, the secreted EGF precursor is capable of activating the intrinsic tyrosyl kinase activity of the EGF receptor. Our results demonstrate that the soluble form of the precursor is generated from the membrane-anchored form by a processing step that takes place at the cell surface and involves truncation of the cytoplasmic and transmembrane domains of the intact EGF precursor. The findings support the hypothesis that the secreted 160- to 170-kilodalton EGF glycoprotein that accumulates in urine and milk is proteolytically derived from the plasma membrane-spanning precursor expressed in the kidney and mammary gland.

3T3 Cells↗
PubMed2000

Murine colonic mucosa hyperproliferation. I. Elevated CFTR expression and enhanced cAMP-dependent Cl(-) secretion.

Fluid transport in the large intestine is mediated by the cystic fibrosis gene product and cAMP-dependent anion channel cystic fibrosis transmembrane conductance regulator (CFTR). cAMP-mediated Cl(-) secretion by gastrointestinal cell lines in vitro has been positively correlated with the insertion of CFTR into the apical membrane of differentiated senescent colonocytes and negatively correlated with the failure of CFTR to insert into the plasma membrane of their undifferentiated proliferating counterparts. In native tissues, this relationship remains unresolved. We demonstrate, in a transmissible murine colonic hyperplasia (TMCH) model, that (8-fold) colonocyte proliferation was accompanied by increased cellular CFTR mRNA and protein expression (8.3- and 2.4-fold, respectively) and enhanced mucosal cAMP-dependent Cl(-) secretion (2. 3-fold). By immunofluorescence microscopy, cellular CFTR expression was restricted to the apical pole of cells at the base of the epithelial crypt. In contrast, increased cellular proliferation in vivo led to increases in both the cellular level and the total number of cells expressing this anion channel, with cellular CFTR staining extending into the crypt neck region. Hyperproliferating colonocytes accumulated large amounts of CFTR in apically oriented subcellular perinuclear compartments. This novel mode of CFTR regulation may explain why high endogenous levels of cellular CFTR mRNA and protein within the TMCH epithelium were not matched with larger increases in transmucosal CFTR Cl(-) current.

Animals↗
PubMed1987

Acid pH enhances the effects of taurodeoxycholate on water and solute transport in the human and rat jejunum.

The relative rate of unspecific binding of bile acids to brush border membrane vesicles resembles their relative potencies as intestinal secretagogues. This interaction of bile acids with brush border membranes is enhanced in an acid environment. We, therefore, studied the effects of taurodeoxycholate and taurocholate on water and solute transport at pH 7.6 and pH 4.0 in the human and rat jejunum. Five mM taurodeoxycholate induced significantly greater fluid secretion in the human jejunum at pH 4.0 than at pH 7.6 (p less than 0.02; n = 5), 10 mM taurocholate (n = 4) had no effect at either pH. In the rat 15 mM taurodeoxycholate at pH 4.0 induced greater fluid secretion (p less than 0.01; n = 6), released more phospholipid (p less than 0.001; n = 4) and enhanced absorption of mannitol more than at pH 7.6 (p less than 0.05; n = 6). In contrast fluid secretion and release of phospholipids induced by Triton X-100 were not affected by pH (n = 6), nor was fluid secretion induced by cholera toxin (n = 8). The data suggest that the enhancement of the secretory effect of taurodeoxycholate in an acid environment is due to its increased interaction with the mucosal surface, and support the concept that the ability of detergents to interact with the intestinal brush border membrane determines their effectiveness as intestinal secretagogues.

Animals↗
PubMed1982

The role of buffer anions and protons in secretion by the rabbit mandibular salivary gland.

1. The role of extracellular HCO3- and H+ in the formation of primary saliva and its subsequent modification by the glandular ducts has been investigated in the isolated perfused mandibular salivary gland of the rabbit. 2. Variation of extracellular HCO3- concentration between 12.5 and 50.0 mmol/l was without effect on salivary flow rate or on Na+ and K+ excretion, even though salivary HCO3- (and Cl-) content altered with changes in the extracellular concentration of the two anions. 3. Complete replacement of perfusate HCO3- by Cl- reduced fluid secretion by 34% and almost abolished ductal Na+ absorption. However, when extracellular pH was controlled by replacing HCO3- with the hydrophilic HEPES buffer, fluid secretion but not ductal Na+ absorption was restored to normal. 4. Complete replacement of exogenous HCO3- with acetate increased fluid secretion by 110% and also stimulated ductal Na+ absorption. This effect did not appear to be related to changes in cell pH and remains unexplained. Acetate entered the saliva in concentrations comparable to those seen for HCO3- in control experiments. 5. Salivary secretion showed an almost linear dependence on extracellular pH, rising from 14% of control (pH 7.4) levels at pH 6.2 to 130% at pH 7.8. Ductal Na+ absorption showed similar pH dependence. 6. Carbonic anhydrase inhibitors did not affect fluid secretion rates (except when supramaximal doses of ACh were used to evoke secretion) but they did cause a large reduction in salivary HCO3- output. In glands perfused with acetate rather than HCO3-, carbonic anhydrase inhibitors had no effect on excretion of fluid, acetate or metabolically derived HCO3-. Duct perfusion studies suggested that the effect of the inhibitors on HCO3- output was at the site of primary secretion rather than at the ductal site of HCO3- transport.

Animals↗
PubMed2003

K(+) transport in Malpighian tubules of Tenebrio molitor L: a study of electrochemical gradients and basal K(+) uptake mechanisms.

Malpighian tubules of the mealworm Tenebrio molitor were isolated for intracellular measurement of basolateral (V(bl)) and, indirectly, apical (V(ap)) membrane potentials. In control Ringer (50 mmol l(-1) K(+), 140 mmol l(-1) Na(+)), V(bl) was 24 mV, cell negative, and V(ap) was 48 mV, cell negative with reference to the lumen. Ion substitution experiments involving K(+) and Na(+) indicated that both V(bl) and V(ap) were sensitive to the bathing K(+) concentration, with the change in V(ap) being 60-77% that of V(bl). A 10-fold drop in bath [K(+)] irreversibly decreased fluid secretion rates from 6.38+/-0.95 nl x min(-1) (mean +/- S.E.M.) to 1.48+/-0.52 nl x min(-1) (N=8). In the presence of 6 mmol l(-1) Ba(2+), a blocker of basal K(+) channels, fluid secretion rates reversibly decreased and the hyperpolarization of both V(bl) and V(ap) seen in 50 mmol l(-1) and 140 mmol l(-1) K(+) indicated a favourable electrochemical gradient for basal K(+) entry. In 5 mmol l(-1) K(+), Ba(2+) induced two different responses: V(bl) either hyperpolarized by approximately 10 mV or depolarised by approximately 14 mV, according to the electrochemical gradient for K(+), which was either inward or outward in low bath [K(+)]. Rubidium, a 'permeant' potassium substitute, caused a hyperpolarization of V(bl), indicating the specificity of K(+) channels found in Tenebrio tubule cells. Other possible K(+) uptake mechanisms located in the basolateral membrane were investigated. Blocking of the putative electroneutral Na(+)/K(+)/2Cl(-) cotransporter by 10 micromol l(-1) bumetanide reversibly decreased fluid secretion rates, with no detectable change in membrane potentials. Ouabain (1 mmol l(-1)), an Na(+)/K(+)-ATPase inhibitor, irreversibly decreased fluid secretion rates but had no effect on electrical potential differences either in the absence or presence of Ba(2+). The results implicate K(+) channels, the Na(+)/K(+)/2Cl(-) contransporter and the Na(+)/K(+)-ATPase in basal K(+) and fluid transport of Tenebrio tubule cells.

Animals↗
PubMed1992

5-HT receptor antagonists and heat-stable Escherichia coli enterotoxin-induced effects in the rat.

The effect of heat-stable E. coli enterotoxin on intestinal fluid secretion is commonly considered to be mediated by stimulation of mucosal cyclic guanosine monophosphate (cGMP). It was demonstrated recently that 5-hydroxytryptamine (5-HT) acts as an important mediator in cholera toxin-induced fluid secretion. To elucidate the possible involvement of 5-HT in the secretory response to heat-stable E. coli enterotoxin, in vivo experiments were performed in the rat jejunum. The inhibitory effects of the 5-HT2 receptor antagonist ketanserin, the 5-HT3 receptor antagonist tropisetron and indomethacin were studied in heat-stable E. coli enterotoxin-induced fluid secretion. Tropisetron and ketanserin (100 micrograms/kg each) alone only partially reduced the secretory effect of the toxin. However, in combination, the two blockers (100 plus 100 micrograms/kg) significantly reduced and at 200 plus 200 micrograms/kg totally abolished heat-stable E. coli enterotoxin-induced secretion without influencing the enterotoxin-induced increase in cGMP. Pretreatment with indomethacin (10 mg/kg) reduced the secretory response to the enterotoxin by about 50%. These results support the concept that 5-HT is an important mediator in intestinal fluid secretion induced by heat-stable E. coli enterotoxin. The enterotoxin may use 5-HT to stimulate prostaglandin formation via 5-HT2 receptors and to activate neuronal structures via 5-HT3 receptors.

Animals↗
PubMed1995

Effect of hypoxia on reflex responses of tracheal submucosal glands.

The effects of moderate sustained normocapnic hypoxia on tracheal submucosal gland reflex responses were studied. Experiments were performed in anesthetized, paralyzed, and mechanically ventilated dogs. The changes in the number of secreting glands and volume of secreted fluid in the subsequent period of time were recorded after 15-30 min of controlled ventilation with room air [arterial PO2 (PaO2) 86 +/- 3 Torr], hypoxic gas mixture (PaO2 49 +/- 4 Torr), or 100% O2 (PaO2 339 +/- 39 Torr), under isocapnic and isohydric conditions. The hillocks method was used to quantify the changes in submucosal gland secretion. The changes in secretion 30 s after stimulation of pulmonary C-fiber receptors by right atrial injection of capsaicin (10 micrograms/kg; n = 10) were markedly lower during moderate hypoxia than in normoxia or hyperoxia. Differences in the number of liquid droplets and the volume of secreted fluid were statistically significant (P < 0.05 and P < 0.001, respectively). Stimulation of airway rapidly adapting receptors by lung deflation increased airway secretion; the number of "hillocks" and the volume of secreted fluid were lower in hypoxic than in hyperoxic state. Differences between response curves for the number of glands activated and secreted volume were statistically significant (P < 0.05 and P < 0.001). The number of glands activated by substance P given locally by arterial infusion was not affected by the state of oxygenation, but the calculated volume of secreted fluid was lower during the hypoxic state than under hyperoxic condition (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effects of amphotericin B and cholera toxin on intestinal transport in the rat. An in vivo model for the effects of dihydroxy bile acids and fatty acids on intestinal transport.

In vivo perfusion experiments were performed in the rat jejunum and colon to test the hypothesis that the changes in intestinal solute transport induced by dihydroxy bile acids and fatty acids are the result of the combined effects of fluid secretion and enhancement of mucosal permeability. The hypothesis predicts that absorption of organic solutes will be reduced in inverse relationship to the absorption rates under control conditions and that absorption of small, nonabsorbable solutes such as mannitol will be enhanced by these agents. Fluid secretion was induced either by administering cholera toxin or by increasing the osmolality of the perfusion solution to 365 mOsm/L. Permeability was enhanced by adding amphotericin B, 50 micrograms/ml, to the perfusion solutions. The isotonic perfusion solutions contained 11.2 mM glucose and 4 mM triethylene, tetraethylene, pentaethylene, and hexaethylene glycol or mannitol as probes of passive permeability. In the jejunum cholera toxin induced fluid and electrolyte secretion and reduced organic solute absorption to a small but significant degree (p less than 0.05). Amphotericin B alone enhanced absorption of organic solutes, water, and electrolytes (p less than 0.01). In the presence of fluid secretion induced by an osmotic load, only absorption of triethylene and pentaethylene glycol was reduced. Addition of amphotericin B after exposure to cholera toxin or to the hypertonic solutions resulted in a further significant reduction of absorption of glucose and ethylene glycols (p less than 0.05). The combination of amphotericin B and cholera toxin resulted in enhanced absorption of mannitol (p less than 0.02). Similarly, 5 mM deoxycholate enhanced jejunal absorption of mannitol (p less than 0.01) and reduced the absorption of glucose and the low-molecular-weight ethylene glycols (p less than 0.01). In the colon the administration of amphotericin B after the exposure to cholera toxin resulted in enhanced absorption of glucose (p less than 0.05) in spite of continuing fluid secretion. The combination of fluid secretion and enhancement of mucosal permeability, therefore, reproduced all in vivo effects of bile acids and fatty acids on intestinal transport of organic solutes.

Amphotericin B↗
PubMed1975

Effects of indomethacin on intestinal secretion, prostaglandin E and cyclic AMP: evidence against a role for prostaglandins in cholera toxin-induced secretion.

The effects of indomethacin on intestine mucosal cAMP, intestinal fluid secretion, and mucosal and fluid PGE were studied in rabbits in vivo following challenge with cholera toxin. Indomethacin had no effect on cholera toxin-induced fluid secretion or cAMP accumulation. Inhibition of PGE synthesis was achieved by the administration of two but not one injection of indomethacin. These studies provide evidence against a role for PGE in mediating cholera toxin-induced secretion and point out the need to measure prostaglandin levels when using prostaglandin synthetase inhibitors in vivo.

Animals↗
PubMed2005

Congenital diaphragmatic hernia prevents absorption of distal air space fluid in late-gestation rat fetuses.

We hypothesized that congenital diaphragmatic hernia (CDH) may decrease distal air space fluid absorption due to immaturity of alveolar epithelial cells from a loss of the normal epithelial Na+ transport, as assessed by amiloride and epithelial Na+ channel (ENaC) and Na-K-ATPase expression, as well as failure to respond to endogenous epinephrine as assessed by propranolol. Timed-pregnant dams were gavage fed 100 mg of nitrofen at 9.5-day gestation to induce CDH in the fetuses, and distal air space fluid absorption experiments were carried out on 22-day gestation (term) fetuses. Controls were nitrofen-exposed fetuses without CDH. Absorption of distal air space fluid was measured from the increase in 131I-albumin concentration in an isosmolar, physiological solution instilled into the developing lungs. In controls, distal air space fluid absorption was rapid and mediated by beta-adrenoceptors as demonstrated by reversal to fluid secretion after propranolol. Normal lung fluid absorption was also partially inhibited by amiloride. In contrast, CDH fetuses continued to show lung fluid secretion, and this secretion was not affected by either propranolol or amiloride. CDH lungs showed a 67% reduction in alpha-ENaC and beta-ENaC expression, but no change in alpha1-Na-K-ATPase expression. These studies demonstrate: 1) CDH delays lung maturation with impaired distal air space fluid absorption secondary to inadequate Na+ uptake by the distal lung epithelium that results in fluid-filled lungs at birth with reduced capacity to establish postnatal breathing, and 2) the main stimulus to lung fluid absorption in near-term control fetuses, elevated endogenous epinephrine levels, is not functional in CDH fetuses.

Absorption↗
PubMed1997

Exocrine pancreatic function in rats after acute pancreatitis.

The present studies were performed to evaluate pancreatic exocrine function in rats during the early stage of acute pancreatitis in two models: one is edematous pancreatitis induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals and the other is hemorrhagic pancreatitis induced by retrograde infusion of 0.4 ml/kg body weight of 3% sodium taurocholate (NaTc) into the pancreatic duct. Secretory studies were performed in vivo under urethane anesthesia at various times after induction of acute pancreatitis. Basal pancreatic fluid secretion was significantly elevated after induction of acute pancreatitis in both the cerulein and the NaTc models, reaching the peak level on postpancreatitic days 1 and 3, respectively. In both models of rats, a stepwise increasing dose of cerulein was unable to cause a further increase in fluid secretion above the basal level, whereas it caused a dose-dependent increase in protein output in both models, although the responsiveness and the sensitivity were markedly reduced compared with the controls. In contrast to cerulein, secretin caused a dose-dependent increase in fluid secretion in both models of pancreatitis. In cerulein-induced postpancreatitic rats, secretin also caused a dose-dependent increase in protein output and bicarbonate concentration, but it had only a small effect at certain doses in NaTc-induced postpancreatitic rats. These results indicate that basal pancreatic fluid secretion was greatly increased but the secretory response to cerulein stimulation was reduced in acute pancreatitis early after the onset but was not reduced to secretin stimulation and that protein output and bicarbonate concentration were reduced depending on the severity of pancreatitis (NaTc-pancreatitis > cerulein-pancreatitis.

Acute Disease↗
PubMed1997

cAMP modulation of a Ca2+-dependent K+ conductance in rat submandibular acinar cells.

Rat submandibular acinar cells exhibit a tetraethylammonium (TEA)-insensitive, Ca2+-activated K+ conductance, which may play an important role in Ca2+-dependent fluid secretion by this gland (T. Ishikawa, M. Murakami, and Y. Seo. Pfluegers Arch. 428: 516-525, 1994; T. Ishikawa and M. Murakami. Pfluegers Arch. 429: 748-750, 1995). We have now investigated whether this conductance would be modified during the potentiation of Ca2+-activated fluid secretion by an adenosine 3',5'-cyclic monophosphate (cAMP)-mediated mechanism in the rat submandibular gland. In isolated, vascularly perfused rat submandibular gland, we found that the adenylate cyclase activator forskolin (10 and 30 microM) enhanced a transient initial phase of a biphasic fluid secretion induced by the Ca2+ ionophore A-23187 (3 microM). We also unexpectedly found that forskolin reduced a smaller sustained phase of the secretion. The dual effects of forskolin were mimicked by the application of the cocktail of 3-isobutyl-1-methylxanthine (IBMX) (0.1 mM) and dibutyryl cAMP (DBcAMP) (0.1 and 0.5 mM). Basolateral K+ efflux studies showed that 1) forskolin significantly enhanced a large transient net K+ efflux induced by A-23187 in a dose-dependent manner; 2) the forskolin-induced enhancement was also mimicked by a cocktail of IBMX and DBcAMP; and 3) the A-23187-induced K+ efflux enhanced by these agents was not inhibited by TEA (5 or 10 mM), a concentration known to completely block Ca2+ voltage-dependent large-conductance K+ channels (maxi-K+ channels). With use of microspectrofluorometry with fura 2, we then showed that an increase in cytosolic Ca2+ concentration induced by the nonfluorescent, brominated derivative 4-bromo-A-23187 (3 microM) was not altered by forskolin (30 microM) in freshly isolated rat submandibular acinar cells. With use of whole cell patch-clamp techniques, we demonstrated that a TEA-insensitive K+ conductance induced by A-23187 in cells dialyzed with pipette solutions containing cAMP (0.1 mM) was significantly larger than that in cells treated with control pipette solutions. Taken together, these results indicate that potentiation of the Ca2+-activated fluid secretion by a cAMP-mediated mechanism is accompanied by potentiation of a TEA-insensitive, Ca2+-activated K+ conductance in this gland.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Cholera toxin induces prostaglandin synthesis via post-transcriptional activation of cyclooxygenase-2 in the rat jejunum.

The mechanisms of diarrhea in Asiatic cholera have been studied extensively. Cyclic AMP, 5-hydroxytryptamine, prostaglandins, and the function of neuronal structures have been implicated in the pathogenesis of cholera. To elucidate the role of the different isoforms (COX-1 and COX-2) of cyclooxygenase in cholera toxin (CT)-induced fluid secretion and intraluminal prostaglandin E(2) (PGE(2)) release in the rat jejunum in vivo, the effects of the COX-2 inhibitors NS-398 ([N-(2-cyclohexaloxy-4-nitrophenyl)methanesulfonamide]) and DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone], and of the COX-1 inhibitor SC-560, were studied. Net fluid transport was measured gravimetrically and PGE(2) by radioimmunoassay. COX-1 and COX-2 mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and COX-2 protein by Western blot analysis in mucosal scrapings. CT caused profuse net fluid secretion in all control rats. The COX-2 inhibitors NS-398 and DFU, but not the COX-1 inhibitor SC-560 or dexamethasone, dose-dependently inhibited CT-induced fluid secretion and PGE(2) release. RT-PCR showed expression of COX-1 and of COX-2 mRNA in control rats. CT did not induce an increase and dexamethasone did not reduce COX-2 mRNA, whereas lipopolysaccharide caused a marked induction of COX-2 mRNA, which was inhibited by dexamethasone. A weak band of COX-2 protein was observed in controls; however, CT enhanced COX-2 levels, which remained unaffected by dexamethasone. It can be assumed that post-transcriptional modulation is responsible for CT-induced increase in COX-2 protein. COX-1 does not seem to be involved. Therefore, PGE(2) produced by COX-2 seems to be responsible for the profuse fluid secretion induced by CT, and COX-2 appears to be a specific target for the treatment of Asiatic cholera.

Animals↗
PubMed1989

Vasoactive intestinal peptide in the normal and inflamed feline gallbladder.

Intravenous infusion of vasoactive intestinal peptide (VIP) causes gallbladder mucosal fluid secretion by an action on epithelial cell receptors in the cat. Gallbladder fluid secretion is observed also in experimental cholecystitis and this secretion is abolished when the intramural gallbladder nerves are blocked. In the present study, immunoreactive VIP was detected in the gallbladder contents (29 +/- 5 (S.E.M.) pM) in the obstructed lumen of the gallbladder in cats with experimental cholecystitis and gallbladder mucosal fluid secretion, but not in the normal feline gallbladder. During luminal perfusion of the gallbladder in vivo, the calculated secretion of VIP into the gallbladder lumen in animals with experimental cholecystitis was significantly higher (0.31 +/- 0.08 (S.E.M.), pmol/h) than in controls (0.11 +/- 0.02 (S.E.M.), pmol/h) while plasma levels of VIP were similar. Recovery of exogenously administered VIP was similar in normal and inflamed gallbladders. The present results support the hypothesis that intramural VIP-releasing nerve fibers may be activated in cholecystitis.

Animals↗
PubMed1993

A comparison of the effects of two putative diuretic hormones from Locusta migratoria on isolated locust malpighian tubules.

Previous work has shown that a peptide related to arginine vasopressin is present in the suboesophageal ganglion of the locust, Locusta migratoria. This peptide was determined to be an anti-parallel dimer of the nonapeptide Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH2 and was reported to stimulate cyclic AMP production and fluid secretion in a combined Malpighian tubules and midgut preparation from locusts. For these reasons the peptide has been called the arginine-vasopressin-like insect diuretic hormone (AVP-like IDH). Recently, a second diuretic peptide (Locusta-DP), which is related to corticotropin releasing factor, has been identified: this is a potent stimulant of fluid secretion and cyclic AMP production by isolated locust tubules. Because water balance in insects is likely to be controlled by a cocktail of hormones acting on both Malpighian tubules and hindgut, this study directly compares the activity of these two peptides in fluid secretion and cyclic AMP production bioassays on one target organ, the isolated Malpighian tubule of Locusta migratoria. Locusta-DP was synthesised directly, whereas the dimeric AVP-like IDH was obtained by oxidation of a synthetic nonapeptide monomer. Products were separated by RP-HPLC and their structures unequivocally confirmed by enzymatic digestion, sequence analysis and electrospray mass spectrometry. We show that Locusta-DP causes strong stimulation of fluid secretion and cyclic AMP production, whereas the AVP-like IDH has no effect in either assay. These findings are discussed in the light of recent work on the anatomy and physiology of the vasopressin-like immunoreactive (VPLI) neurones in the suboesophageal ganglion of Locusta migratoria, the proposed source of the AVP-like peptide.

Amino Acid Sequence↗
PubMed1987

Atrial natriuretic factor and exocrine pancreas: effects on the secretory process.

Immunoreactive atrial natriuretic factor (ANF) has recently been identified in pancreatic acinar cells. The current study therefore, was, designed to ascertain whether the atrial peptide exercises any biological effects on the exocrine pancreas. When isolated rat pancreatic acinar cells were incubated with rat ANF (8-33), a concentration-dependent increase in cGMP synthesis was observed (EC50 about 5 X 10(-9) M) with the peak response occurring within 2.5 min of exposure of the cells to the peptide. ANF did not affect basal or secretagogue (carbachol +/- DbcAMP, CCK-OP, or forskolin)-induced amylase secretion from acinar cells, nor did it affect [3H]thymidine incorporation into DNA or [3H]leucine incorporation into trichloroacetic acid-precipitable protein. ANF was also infused intravenously (0.01-0.25 micrograms/min) in rabbits with cannulated pancreatic ducts, and the peptide stimulated a dose-dependent secretion of cGMP into pancreatic juice. ANF, by itself, did not affect protein or fluid secretion from rabbit pancreas; when co-infused with secretin (0.1 CU/min), which is not an acinar cell secretagogue in rabbits, ANF increased fluid secretion in one of three animals tested. The data suggest that acinar cells possess functional ANF receptors, whose activation results in both synthesis and secretion of cGMP. Intra-acinar cell cGMP is not involved in the enzyme secretory process. Secreted nucleotide is not co-released with digestive hydrolases, and does not, by itself, appear to have an intraluminal effect on fluid secretion. The mechanism by which acinar cells secrete cGMP into pancreatic juice as well as the biological significance of intracellular (acinar), and extracellular (intraluminal) cGMP remain to be elucidated.

Amylases↗
PubMed1994

Evidence for redox cycling of diquat in rat small intestine.

It has previously been established that acute diquat (1,1'-ethylene, 2,2'-bipyridilium) toxicity in the rat is associated with stimulation of net fluid secretion into the gastrointestinal tract. We have examined the possibility that the mechanism of diquat toxicity in the small intestine involves redox cycling of the bipyridyl leading to a disturbance of biochemical function and oxidative stress. Experiments performed in vitro showed that diquat (10 microM to 1 mM) produced an increase in activity of the pentose phosphate pathway in rat small intestinal tissue slices, suggesting that there was oxidation of NADPH even at concentrations of diquat which do not cause intestinal fluid secretion in anaesthetized rats. When the effect of diquat on pentose phosphate activity was measured in rats in situ at a dose which causes maximal fluid secretion [50 mM diquat dibromide (DQBr2)], production of 14CO2 from [1-14C]-glucose increased by 278 +/- 28% (N = 4) within 1 hr of exposure to diquat. Under these same conditions, the tissue content of NADPH in the proximal small intestine was significantly depleted, though there was no corresponding increase in NADP+ concentration. Diquat had no effect on tissue concentrations of either the reduced or oxidized forms of NAD. It is likely that NADPH oxidation at low diquat concentrations can be adequately compensated for by mechanisms within the tissue which protect against oxidative stress. However, the data also suggest that diquat-induced fluid secretion in the rat small intestine is associated with redox cycling of bipyridyl leading to depletion of NADPH.

Animals↗
PubMed1989

Lacrimal fluid and electrolyte secretion: a review.

Lacrimal gland fluid is an important component of the precorneal tear film. The rate of lacrimal gland fluid secretion is controlled primarily by parasympathetic innervation, and it is, apparently, modulated by sympathetic innervation. Lacrimal gland fluid is produced in two stages, secretion of a primary fluid which resembles an isotonic ultrafiltrate of plasma in the acinus-early intercalated duct region, and secretion of a KCl-rich fluid in subsequent ductal elements. Little is known about the electrolyte transport mechanisms of the ductal epithelia. Recent work using a variety of techniques, including tracer flux measurements, intracellular electrical recording, intracellular ion activity measurements, patch clamping, and analytical subcellular fractionation, supports a model for transcellular Cl-secretion in the acinus which involves Cl--selective channels in the apical plasma membrane and an array of Na+/H+ antiporters, Cl-/HCO3-antiporters, K+ channels, and Na,K-ATPase in the basal-lateral plasma membrane.

Animals↗