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PubMed1978

Inhibition by morphine of prostaglandin-stimulated fluid secretion in rat jejunum.

1 Anesthetized rats (225 to 300 g) were used to study the inhibitory effect of morphine on fluid secreted by the small intestine. 2 Small intestinal fluid secretion was stimulated by infusion of prostaglandin E1 (PGE1) into the aortic arch, the jejunum being more sensitive than the ileum. Infusion of PGE1 2 microgram/min caused maximal net fluid secretion in the jejunum but inhibited net fluid absorption in the ileum. 3 Morphine caused a dose-related inhibition of maximal PGE1-stimulated fluid secretion in the jejunum. At the higher doses of morphine used (5 to 20 mg/kg) the fluid transporting function of the jejunum was restored almost to normal net absorption. 4 The inhibitory effect of morphine on PGE1-stimulated fluid secretion was antagonized by naloxone. Naloxone caused a parallel shift to the right of the dose-response curve for morphine. 5 Two other narcotic analgesics were assayed relative to morphine and their descending order of potency was oxymorphone greater than morphine greater than pethidine. 6 It is suggested that the antisecretory effect of morphine in the small intestine may contribute to its efficacy as an anti-diarrhoeal drug. Further studies on the rat jejunum may show it to be a useful model for predicting narcotic drug activity and as such, may give some insight into the mechanisms of action of these drugs.

Animals↗
PubMed1998

Inhibition of salivary fluid secretion by occlusion of the intercellular space.

The effects of HCO3- on fluid secretory rate, cell volume and tissue structure were studied in perfused submandibular salivary glands under hyposmotic conditions (240 mosM). Fluid secretion was elicited by acetylcholine (ACh) in a hyposmotic HCO3(-)-free solution. Upon switching the perfusate from the HCO3(-)-free to the HCO3(-)-containing solution during ACh stimulation, the fluid secretory rate exhibited a small transient increase followed by a sharp decrease. ACh stimulation evoked rapid cell shrinkage in the absence of HCO3-, but upon switching from the HCO3(-)-free to the HCO3(-)-containing solution during ACh stimulation, the acinar cells exhibited increases in volume. In laser confocal microscopic examination of isolated acini, fluorescence of lucifer yellow was detected in the lateral intercellular spaces during ACh stimulation in the absence of HCO3-, but not in the presence of HCO3-. Electron microscopic examination revealed similar findings. We propose that the occlusion of the lateral intercellular space induced by cell swelling may result in an increase in the resistance to fluid flow in the space and consequently a decrease in the fluid secretion rate. Maintenance of an open lateral intercellular space may be an important requirement for fluid secretion. These observations suggest that a paracellular pathway may play a significant role in salivary fluid secretion.

Acetylcholine↗
PubMed2003

Nucleotide-induced restoration of conjunctival chloride and fluid secretion in adenovirus type 5-infected pigmented rabbit eyes.

We evaluated the role of extracellular UTP and other nucleotides in the regulation of chloride (JCl) and fluid secretion (JCl) across the pigmented rabbit conjunctiva. Jv was determined in freshly excised conjunctival tissues mounted between two buffer reservoirs maintained in an enclosed environment at 37 degrees C. Short circuit current (Isc) and 36Cl flux were measured using modified Ussing-type chambers. Fluid flux measurements were made with a pair of capacitance probes. After observing the baseline for 15 to 30 min, fluid flux was measured in the presence of mucosally applied nucleotides (10 microM) for a period of 30 min. Mucosal application of 10 microM each of UTP, UDP, ATP, ADP, AMP, adenosine, and ATP-gamma-S transiently stimulated fluid secretion across the conjunctiva to a significant extent for 10 to 15 min. Other nucleotides did not show any significant effect. The stimulation of fluid secretion correlated well with the stimulation in Isc (r2 = 0.85). UTP (0.1-1000 microM) led to a maximal increase in fluid secretion by 11.72 +/- 0.48 microl/(h x cm2) with an EC50 value of 10.39 +/- 1.08 microM. ATP (0.1-1000 microM) caused a maximal increase in fluid secretion by 11.89 +/- 0.88 microl/(h x cm2) with an EC50 value of 17.23 +/- 2.63 microM. Adenovirus type 5 (Ad5) infection significantly decreased both net 36Cl secretion across the conjunctiva by approximately 56% and the rate of fluid secretion by approximately 56%. UTP (10 microM), but not 1 mM 8-bromo-cAMP, was able to elicit a normal stimulatory response in the Ad5-infected tissues. In conclusion, mucosal application of purinergic nucleotides may be therapeutically important in restoring ion and fluid secretion in the diseased conjunctiva.

Adenosine↗
PubMed1991

Characteristics of fluid secretion from isolated rat pancreatic ducts stimulated with secretin and bombesin.

1. Micropuncture techniques were used to study the cellular mechanisms of fluid secretion by interlobular ducts isolated from the pancreas of copper-deficient rats. 2. Perifusing ducts with a calcium-free buffer containing 5 mM-EGTA reduced the volume of fluid secreted in the presence of 10 nM-bombesin by 62%, whereas fluid secretion measured in the presence of 10 nM-secretin was reduced by only 26%. 3. The anion selectivities of the fluid secretions evoked by secretin and bombesin were different. The anion sequence for secretin was: Br- = I- = NO3- = Cl- (1.0) much greater than thiocyanate = gluconate (0.3); whereas the sequence for bombesin was: Br- = Cl- (1.0) greater than I- = NO3- (0.6) greater than thiocyanate = gluconate (approximately 0.3). 4. SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid; mM), reduced fluid secretion measured in the presence of bombesin by 61%, but had no effect on the response to secretin. 5. The K+ channel blockers, barium (3 mM) and tetraethylammonium (TEA; 10 mM), inhibited fluid secretion measured in the presence of both secretin and bombesin by between 52 and 66%. 6. From these results, we conclude that secretin and bombesin may utilize different intracellular signalling pathways and, furthermore, may activate different anion secretory mechanisms within the pancreatic ductal epithelium. However, the effect of the potassium channel blockers is consistent with both peptides activating secretory mechanisms which are electrogenic, and which depend for their operation on potassium efflux across the basolateral membrane of the duct cell.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1982

Inhibition of Escherichia coli heat-stable enterotoxin effects on intestinal guanylate cyclase and fluid secretion by quinacrine.

Enterotoxigenic Escherichia coli may produce a heat-stable enterotoxin (ST) that causes diarrheal disease in humans and in animals ST activates particulate guanylate cyclase in intestinal mucosal cells and causes intestinal fluid secretion. In this study, we examined the effects of quinacrine on ST activation of guanylate cyclase and ST-mediated intestinal fluid secretion. Quinacrine significantly reduced ST activation of particulate guanylate cyclase in rat intestinal tissue. Additionally, quinacrine reduced ST-mediated fluid secretion in a rat intestinal loop assay (P less than 0.05). In the suckling mouse model, subcutaneous quinacrine (0.1 mumole/mouse) reduced ST-induced fluid secretion at a submaximally effective dose of the toxin, but it did not reduce ST-mediated fluid secretion at a near maximally effective dose. Quinacrine (0.1 mumole/mouse) did not significantly reduce intestinal fluid secretion induced by the analog of cyclic GMP, 8-bromo cyclic GMP. However, at a higher concentration of quinacrine (1 mumole/mouse), significant inhibition of 8-bromo cyclic GMP-induced secretion was observed. Inhibition by the antimalarial agent quinacrine of ST-induced fluid secretion, by a block prior to guanylate cyclase activation, suggests a possible role for a phospholipase early in the sequence of events of ST activation of guanylate cyclase. The results suggest that ST may activate membrane phospholipases prior to ST activation of guanylate cyclase.

Animals↗
PubMed1992

Developing bronchopulmonary epithelium of the human fetus secretes fluid.

We studied human fetal lung tissue in submersion organ culture to determine whether the bronchopulmonary epithelium secretes fluid during development. In this system the acinar tubules continued to grow, secrete fluid, and become progressively dilated. Baseline transepithelial potential differences (psi t) of -0.5 to -11 mV (mean, -3.8 mV, lumen negative, n = 27) were measured with microelectrodes after 3-8 days in culture, suggesting active electrolyte transport. Bumetanide (500 microM), an inhibitor of chloride secretion in other systems, decreased the basal psi t from -5 +/- 1.5 to -3.2 +/- 1.6 (SE) mV (P less than 0.05, n = 6), suggesting that chloride transport contributed to the voltage. Isoproterenol (5 microM) increased the baseline psi t from -5.6 +/- 2.1 to -9.2 +/- 2.5 (SE) mV (P less than 0.05, n = 4). Subsequent addition of bumetanide inhibited the isoproterenol-induced stimulation of the psi t by 20% (P less than 0.05). 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate. (CPT-cAMP, 50 microM) and 3-isobutyl 1-methylxanthine (IBMX, 100 microM) had similar effects, causing an increase in the psi t from -2.2 +/- 0.5 to -8 +/- 1.6 (SE) mV, an effect that was inhibited by the addition of bumetanide (P less than 0.005, n = 6). Both isoproterenol and CPT-cAMP/IBMX produced significant increases in the percentage luminal area of the explants at 12 and 24 h after exposure compared with control. We conclude that 1) the developing bronchopulmonary epithelium (acinar tubules) contributes to lung fluid production in the human fetus, 2) fetal lung fluid secretion is chloride dependent, and 3) chloride secretion and fluid secretion may be stimulated by a beta-agonist and cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Inhibition of 5-hydroxytryptamine- and enterotoxin-induced fluid secretion by 5-HT receptor antagonists in the rat jejunum.

The effects of cholera toxin and heat stable Escherichia coli (E. coli) enterotoxin on intestinal fluid secretion are commonly considered to be mediated by cyclic nucleotides. It was demonstrated recently, by using the 5-hydroxytryptamine (5-HT)2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist tropisetron, that 5-HT acts as an important mediator in cholera toxin- and heat stable E. coli enterotoxin-induced fluid secretion. In the present investigation ketanserin and tropisetron were compared with the newer 5-HT3 receptor antagonists ondansetron and granisetron versus 5-HT-, cholera toxin- and heat stable E. coli enterotoxin-induced fluid secretion in the rat jejunum in vivo. Both ondansetron and granisetron dose-dependently inhibited 5-HT- and enterotoxin-induced fluid secretion. Ketanserin blocked 5-HT-induced fluid secretion, but only diminished enterotoxin-induced effects even at higher doses. Tropisetron inhibited 5-HT- and cholera toxin-induced effects at high dose but only diminished heat stable E. coli enterotoxin-induced effects. We conclude that 5-HT3 receptors, located on enterochromaffin cells and nervous structures, are more important in mediating fluid secretion than 5-HT2 receptors, located on the epithelial cells.

Animals↗
PubMed1983

The dependence of fluid secretion by mandibular salivary gland and pancreas on extracellular calcium.

Acetylcholine-stimulated fluid secretion from the perfused rabbit mandibular salivary gland was inhibited in a biphasic manner when extracellular calcium concentration was reduced in the range 5 X 10(-4) - 10(-5)M. An initial rapid inhibition was followed by partial recovery to a plateau, the level of which depended upon the calcium concentration. Since no recovery was observed during substitution of calcium by strontium, recovery may depend upon an increased membrane permeability to calcium. It is concluded that acetylcholine evokes fluid secretion in this gland by enhancing calcium entry from the extracellular space, an action which can be mimicked by the calcium ionophore A23187. Changes in the electrolyte composition of saliva during calcium-depletion were such as to suggest that ductal reabsorption of sodium and chloride, and secretion of potassium are inhibited as extracellular calcium concentration is reduced. Secretin-stimulated fluid secretion from the cat pancreas was unaffected when perfusate calcium concentration was reduced to 2.5 X 10(-6)M and carbachol-stimulated amylase secretion was only slightly reduced. Since the latter is a calcium-dependent process, the source of calcium is presumably intracellular. In both glands, reducing calcium to 1 X 10(-6)M caused rapid and irreversible inhibition of fluid secretion.

Acetylcholine↗
PubMed1995

Cyst fluid from a murine model of polycystic kidney disease stimulates fluid secretion, cyclic adenosine monophosphate accumulation, and cell proliferation by Madin-Darby canine kidney cells in vitro.

Cyst fluids from subjects with autosomal dominant polycystic kidney disease (ADPKD) cause polarized monolayers of MDCK cells to secrete fluid toward the apical compartment in vitro. To determine the extent to which secretagogue accumulation may be a general feature of polycystic diseases, cyst fluid from mice with a slowly progressive form of hereditary PKD (DBA/2FG-pcy/pcy) was added to polarized MDCK monolayers. Basolateral application of cyst fluids (diluted with culture medium to 15% final concentration) from 13 different animals 16 to 35 weeks old increased the fluid secretion rate from a baseline of 0.023 +/- 0.003 to 0.111 +/- 0.017 microL/cm2/h (P < 0.005). There was a direct relation between the concentration of cyst fluid and the rate of net fluid secretion. The secretory activity of cyst fluid was not altered by pronase treatment or boiling. Cyst fluid (10%) added to the basolateral surfaces of polarized MDCK monolayers for 24 hours increased cell cyclic adenosine monophosphate (AMP) levels from a baseline of 6.3 +/- 0.2 to 17.3 +/- 0.3 pmoles/monolayer (n = 3, P < 0.05). The capacity of cyst fluid to increase cyclic AMP levels was not changed by pronase treatment or boiling. There was a direct relation between the level of cellular cyclic AMP and the rate of transepithelial fluid secretion caused by cyst fluid. Cyst fluid increased thymidine incorporation by Madin-Darby canine kidney (MDCK) cells to an extent equal to that caused by epidermal growth factor and caused MDCK cells to form cysts in collagen matricies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes.

Na+/H+ exchanger (NHE) isoforms play important roles in intracellular pH regulation and in fluid absorption. The isoform NHE3 has been localized to apical surfaces of epithelia and in some tissues may facilitate the absorption of NaCl. To determine whether the apical isoform NHE3 is present in cholangiocytes and to examine whether it has a functional role in cholangiocyte fluid secretion and absorption, immunocytochemical studies were performed in rat liver with NHE3 antibodies and functional studies were obtained in isolated bile duct units from wild-type and NHE3-/- mice after stimulation with forskolin, using videomicroscopic techniques. Our results indicate that NHE3 protein is present on the apical membranes of rat cholangiocytes and on the canalicular membrane of hepatocytes. Western blots also detect NHE3 protein in rat cholangiocytes and isolated canalicular membranes. After stimulation with forskolin, duct units from NHE3-/- mice fail to absorb the secreted fluid from the cholangiocyte lumen compared with control animals. Similar findings were observed in isolated bile duct units from wild-type mice and rats in the presence of the Na+/H+ exchanger inhibitor 5-(N-ethyl-N-isopropyl)-amiloride. In contrast, we could not demonstrate absorption of fluid from the canalicular lumen of mouse or rat hepatocyte couplets after stimulation of secretion with forskolin. These findings indicate that NHE3 is located on the apical membrane of rat cholangiocytes and that this NHE isoform can function to absorb fluid from the lumens of isolated rat and mouse cholangiocyte preparations.

Absorption↗
PubMed1998

Fluid secretion in interlobular ducts isolated from guinea-pig pancreas.

1. Pancreatic HCO3- and fluid secretion were studied by monitoring luminal pH (pHL) and luminal volume simultaneously in interlobular duct segments isolated from guinea-pig pancreas. The secretory rate and HCO3- flux were estimated from fluorescence images obtained following microinjection of BCECF-dextran (70 kDa, 20 microM) into the duct lumen. 2. Ducts filled initially with a Cl--rich solution swelled steadily (2.0 nl min-1 mm-2) when HCO3-/CO2 was introduced, and the luminal pH increased to 8.08. When Cl- was replaced by glucuronate, spontaneous fluid secretion was reduced by 75 %, and pHL did not rise above 7.3. 3. Cl--dependent spontaneous secretion was largely blocked by luminal H2DIDS (500 microM). We conclude that, in unstimulated ducts, HCO3- transport across the luminal membrane is probably mediated by Cl--HCO3- exchange. 4. Secretin (10 nM) and forskolin (1 microM) both stimulated HCO3- and fluid secretion. The final value of pHL (8.4) and the increase in secretory rate (1.5 nl min-1 mm-2) after secretin stimulation were unaffected by substitution of Cl-. 5. The Cl--independent component of secretin-evoked secretion was not affected by luminal H2DIDS. This suggests that a Cl--independent mechanism provides the main pathway for luminal HCO3- transport in secretin-stimulated ducts. 6. Ducts filled initially with a HCO3--rich fluid (125 mM HCO3-, 23 mM Cl-) secreted a Cl--rich fluid while unstimulated. This became HCO3--rich when secretin was applied. 7. Addition of H2DIDS and MIA (10 microM) to the bath reduced the secretory rate by 56 and 18 %, respectively. Applied together they completely blocked fluid secretion. We conclude that basolateral HCO3- transport is mediated mainly by Na+-HCO3- cotransport rather than by Na+-H+ exchange.

Adenosine Triphosphate↗
PubMed1999

Vagotomy inhibits the jejunal fluid secretion activated by luminal ileal Escherichia coli STa in the rat in vivo.

BACKGROUND: Escherichia coli heat stable enterotoxin (STa) is a major cause of secretory diarrhoea in humans. AIMS: To assess the effects of instilling STa into the ileum on remote fluid secretion in the jejunum and colon in rats in vivo by a gravimetric technique. METHODS AND RESULTS: Ileal STa (55 ng/ml) stimulated fluid secretion in both ileal and jejunal loops but not in the colon. The fluid secretion induced by ileal STa was inhibited by L-NAME (Nomega-nitro-L-arginine methyl ester, 40 mg/kg intraperitoneally) but not by D-NAME (Nomega-nitro-D-arginine methyl ester). Ileal carbachol (183 mg/ml) instilled into the lumen stimulated ileal secretion but not jejunal secretion, and was unaffected by L-NAME. Capsaicin (10 microM), instilled luminally with STa in the ileum, blocked both the ileal and jejunal fluid secretion. Acute bilateral vagotomy prevented luminal ileal STa from inducing jejunal fluid secretion but not from activating ileal fluid secretion. CONCLUSION: Ileal E coli STa stimulates remote secretion in the rat jejunum but not in the colon, probably by a nitrinergic, vagal reflex mediated by C fibres. This neural pathway will amplify the action of the toxin in its generation of secretory diarrhoea.

Animals↗
PubMed2001

5-hydroxytryptamine strongly inhibits fluid secretion in guinea pig pancreatic duct cells.

We studied the distribution of 5-hydroxytryptamine- (5-HT-) containing cells in the guinea pig pancreas and examined the effects of 5-HT on fluid secretion by interlobular pancreatic ducts. The 5-HT-immunoreactive cells with morphological characteristics of enterochromaffin (EC) cells were scattered throughout the duct system and were enriched in islets of Langerhans. The fluid secretory rate in the isolated interlobular ducts was measured by videomicroscopy. Basolateral applications of 5-HT strongly but reversibly reduced HCO(3)-dependent, as well as secretin- and acetylcholine- (ACh-) stimulated, fluid secretion, whereas 5-HT applied into the lumen had no such effects. Secretin-stimulated fluid secretion could be inhibited by a 5-HT(3) receptor agonist, but not by agonists of the 5-HT(1), 5-HT(2), or 5-HT(4) receptors. Under the stimulation with secretin, 5-HT decreased the intracellular pH (pH(i)) and reduced the rate of pH(i) recovery after acid loading with NH(4)(+), suggesting that 5-HT inhibits the intracellular accumulation of HCO3(-). The elevation of intraductal pressure in vivo reduced secretin-stimulated fluid secretion, an effect that could be attenuated by a 5-HT(3) receptor antagonist. Thus, 5-HT, acting through basolateral 5-HT(3) receptors, strongly inhibits spontaneous, secretin-, and ACh-stimulated fluid secretion by guinea pig pancreatic ducts. 5-HT released from pancreatic ductal EC cells on elevation of the intraductal pressure may regulate fluid secretion of neighboring duct cells in a paracrine fashion.

Acetylcholine↗
PubMed2001

Rabbit conjunctival epithelium transports fluid, and P2Y2(2) receptor agonists stimulate Cl(-) and fluid secretion.

Rabbit conjunctival epithelium exhibits UTP-dependent Cl(-) secretion into the tears. We investigated whether fluid secretion also takes place. Short-circuit current (I(sc)) was 14.9 +/- 1.4 microA/cm(2) (n = 16). Four P2Y(2) purinergic receptor agonists [UTP and the novel compounds INS365, INS306, and INS440 (Inspire Pharmaceuticals)] added apically (10 microM) resulted in temporary (approximately 30 min) I(sc) increases (88%, 66%, 57%, and 28%, respectively; n = 4 each). Importantly, the conjunctiva transported fluid from serosa to mucosa at a rate of 6.5 +/- 0.7 microl x h(-1) x cm(-2) (range 2.1--15.3, n = 20). Fluid transport was stimulated by mucosal additions of 10 microM: 1) UTP, from 7.4 +/- 2.3 to 10.7 +/- 3.3 microl x h(-1) x cm(-2), n = 5; and 2) INS365, from 6.3 +/- 1.0 to 9.8 +/- 2.5 microl. h(-1) x cm(-2), n = 5. Fluid transport was abolished by 1 mM ouabain (n = 5) and was drastically inhibited by 300 microM quinidine (from 6.4 +/- 1.2 to 3.6 +/- 1.0 microl x h(-1) x cm(-2), n = 4). We conclude that this epithelium secretes fluid actively and that P2Y(2) agonists stimulate both Cl(-) and fluid secretions.

Animals↗
PubMed1991

Elevation of resting fluid secretion precedes trophic responses in the rat pancreas following a single oral administration of Camostat.

A single dose of the synthetic proteinase inhibitor, Camostat (FOY-305; 100 mg/kg), was administered orally to rats. Pancreata were isolated and then perfused to examine the change in the level of resting fluid secretion. As early as 6 h after administration of the single dose of Camostat, the resting fluid secretion was significantly elevated. Twelve hours after administration, resting fluid secretion was maximally elevated, whereas contents of trypsinogen, chymotrypsinogen, and amylase per DNA in the pancreas were significantly decreased. After 12 h, the level of resting fluid secretion gradually decreased to the control resting level in contrast to significant increases in contents of the pancreatic enzyme and zymogens, and wet weight in acinar cells. We further examined the mechanism mediating the elevated resting fluid secretion. Our results are compatible with the view that the elevation of resting fluid secretion may be maintained by spontaneous activation of ion transporters: an ouabain-sensitive Na-K ATPase, an amiloride-sensitive Na-H antiporter, and a unique Cl transporter that is insensitive to furosemide, bumetanide, SITS, and DNDS.

Administration, Oral↗
PubMed1976

Fluid secretion in the nephron: Relation to renal failure.

It had been generally accepted that glomerular filtration and tubular reabsorption were the basic modes of fluid transport in mammalian nephrons. Recently, evidence was obtained to indicate that net fluid secretion may occur in mammalian nephrons as well. In the pars recta portion of proximal tubules of rabbit kidney net fluid secretion was observed in vitro in response to PAH and other aryl acids in the peritubular bathing medium. Net fluid secretion appeared to be coupled to the transcellular transport of aryl acid from bath to lumen. Serum from uremic subjects stimulated net fluid secretion in the pars recta in a manner similar to PAH. The accumulation of high levels of endogenous aryl acids may contribute to the general organ dysfunction that is a part of the uremic syndrome of advanced renal insufficiency. Futhermore, there is evidence to suggest that the fluid-secretion phenomenon in association with aryl acids may significantly affect renal excretion and morphology in slow-flow states, in patients with cystic kidney disease, and in obstructive nephropathy.

Aminohippuric Acids↗
PubMed1995

Tachykinin-induced nasal fluid secretion and plasma exudation in the rat: effects of peptidase inhibition.

Substance P (SP) evokes fluid secretion and plasma extravasation when applied to the nasal mucosa of rats. SP and another tachykinin, neurokinin A (NKA), are degraded in vitro by neutral endopeptidase (NEP) and angiotensin-1-converting enzyme (ACE). In this study, NKA or SP were applied locally to the nasal mucosa of rats. Subsequent fluid secretion was measured by a filter paper technique. Plasma exudation was derived as the recovery of intravenous (i.v.) administered 125I-albumin from the fluid-containing filter papers. In order to inhibit enzymatic degradation of the tachykinins by NEP and ACE, the rats were treated with i.v. administered phosphoramidon or captopril respectively or their combination. SP evoked fluid secretion that was augmented by phosphoramidon and further enhanced by adding captopril. NKA evoked nasal fluid secretion less effectively than SP and the effect was unaffected by peptidase inhibition. SP, but not NKA, evoked increased plasma exudation but only after pre-treatment with phosphoramidon.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Interactions between secretin and acetylcholine in the regulation of fluid secretion by isolated rat pancreatic ducts.

1. Interlobular ducts were isolated from the rat pancreas and maintained in short-term tissue culture. Fluid secretion from these isolated ducts was measured using micropuncture techniques, intracellular calcium concentration ([Ca2+]i) by fura-2 microspectrofluorimetry, and cyclic AMP by radioimmunoassay. 2. Applying secretin and ACh simultaneously to ducts caused either a stimulation or an inhibition of fluid secretion depending on the doses employed. 3. The inhibitory effect of secretin and ACh could be relieved by atropine, and by the protein kinase C (PKC) inhibitors staurosporine and 1-(5-isoquinolinylsulphonyl)-2-methyl-piperazine (H-7). 4. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol 12, 13-dibutyrate (PDBu) inhibited secretin-evoked fluid secretion. 5. ACh and TPA also inhibited fluid secretion stimulated by the adenylate cyclase activator, forskolin. 6. Neither secretin nor the PKC activators and inhibitors had any effect on either the increase in [Ca2+]i evoked by ACh or the increase in intracellular cyclic AMP evoked by secretin and forskolin. 7. We conclude that the inhibitory effect of combined doses of secretin and ACh on ductal fluid secretion is probably mediated by PKC at a point in the secretory mechanism distal to the generation of intracellular messengers.

Acetylcholine↗