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The anionic basis of fluid secretion by the rabbit mandibular salivary gland.

The role played by anions in salivary secretion has been studied in experiments on the isolated, perfused mandibular gland of the rabbit, in which perfusate Cl- and/or HCO3- were replaced by other anions. Replacement of Cl- with Br- had no significant effect on salivary secretion rate, but replacement with the other anions tested caused secretory rate to fall, by 38% (I-), 50% (NO3-), 61% (isethionate, ise -), and 66% ( CH3SO4 -), respectively. Replacement of perfusate Cl- with ise - or CH3SO4 - caused the salivary HCO3- concentration to rise up to 4-fold. Replacement with Br- or I- seemed to have little effect on salivary HCO3- concentration but, in contrast to ise -, Br- and I- entered the saliva in concentrations comparable to those of Cl- during control perfusion. In glands perfused with HCO3- and ise -, the addition of methazolamide, an inhibitor of carbonic anhydrase, caused a further 60% drop in secretory rate, but the saliva remained rich in HCO3-. Replacement of perfusate HCO3- with Cl- or ise - had no effect on salivary secretion or composition. Replacement of both HCO3- and Cl- in the perfusate with ise - reduced salivary secretion to less than 2% of control levels. In control glands (i.e. perfused with both HCO3- and Cl-), administration of furosemide, an inhibitor of Na+/Cl- co-transport, reduced the secretion rate and increased salivary HCO3- in a manner indistinguishable from that seen when perfusate Cl- was replaced with ise -. In control perfused glands, administration of SITS (4-acetamido-4'- isothio cyano-2,2'-disulphonic acid stilbene), an inhibitor of Cl-/HCO3- antiports , did not cause any change in salivary HCO3- concentration. Unexpectedly, it induced a significant increase in salivary secretory rate. The results show that salivary secretion depends on two independent transport systems. One is a Cl- -dependent, furosemide-sensitive system, probably a Na+/Cl- symport. The other is an HCO3- -dependent, methazolamide-sensitive system, and is probably an Na+/H+ antiport.

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

Role of plasma filtration in the intestinal fluid secretion mediated by infection with Salmonella typhimurium.

The mechanisms whereby invasive enteropathogens, e.g., Salmonella typhimurium, induce intestinal secretion are largely unknown. Since these organisms penetrate the intestinal epithelium, disrupt the brush border, and evoke an acute inflammatory reaction, increased plasma filtration through a damaged, more permeable epithelium might contribute to the secretory process. To examine this possibility, the plasma-to-lumen clearance of two different sized molecules, [51Cr]albumin and [14C]mannitol, was measured in the in vivo rabbit ileal loop and in vivo rhesus monkey models of salmonellosis. In the rabbit ileal loop model, the clearance of neither molecule was increased when compared to cholera toxin-exposed loops. In the rhesus monkey, clearance of [14C]mannitol into the jejunum, ileum, and colon of Salmonella-infected animals did not differ from the observed in control animals. These data indicate that invasion of the intestinal mucosa by S. typhimurium has not substantially altered the permeability characteristics of the intestinal mucosa and that plasma filtration through a damaged, more permeable mucosa does not contribute to the Salmonella-induced intestinal secretory process.

Animals↗

Net fluid secretion and impaired villous function induced by colonization of the small intestine by nontoxigenic colonizing Escherichia coli.

The role of colonizing bacteria in the small bowel in causing diarrhea remains unclear. We examined whether colonizing, nontoxigenic Escherichia coli could alter small bowel function by determining net water and electrolyte fluxes and sucrase activity in colonized and noncolonized ileal segments by using the reversible-ileal-tie adult rabbit model. Colonization of the ileum with nontoxigenic E. coli for greater than or equal to 72 h at greater than or equal to 10(4)/cm2 was associated with significant functional derangements, as follows: (i) overt liquid diarrhea in 50% of animals colonized at greater than 10(4)/cm2; (ii) reversal of normal net ileal absorption to net secretion of water, sodium, and chloride; and (iii) significant decrease in mucosal sucrase activity. We conclude that small bowel colonization by colonizing, nontoxigenic E. coli impairs water and electrolyte absorption and sucrase activity in the absence of recognized enterotoxin, cytotoxin, invasion, or effacement traits.

Animals↗

Nufenoxole, a new antidiarrhoeal agent, inhibits fluid secretion in the human jejunum.

Nufenoxole is an orally active antidiarrhoeal agent which binds to opioid receptors in the brain and myenteric plexus of the intestine. A perfusion technique has been used to investigate the effect of nufenoxole (1 mg/kg intrajejunally) on water and solute transport stimulated by the secretagogue, dioctyl sodium sulphosuccinate, in the human jejunum in vivo. Nufenoxole reversed the direction of jejunal transport of salt and water from net secretion to net absorption. These changes in water and electrolyte transport were inhibited by intravenous naloxone, the opioid antagonist. Nufenoxole possesses potent antisecretory properties, which are mediated via opioid receptors and may contribute to its antidiarrhoeal action in man.

Adult↗

Choline evokes fluid secretion by perfused rat mandibular gland without desensitization.

The secretomotor action of choline on salivary secretion has been studied in the isolated perfused mandibular gland of the rat. Choline made up in substituted Ringer solutions (Na concentrations of 40, 70, or 100 mM) was an effective secretomotor agonist in the concentration range of 1-100 mM and evoked secretory responses comparable with those of acetylcholine (0.05-1.0 microM) administered at similar Na concentrations. Continuous infusion of choline, in contrast to acetylcholine, did not lead to a fall off in the secretory response (desensitization or tachyphylaxis) until the choline concentration used exceeded approximately 80 mM. The secretomotor action of choline (46 mM) was blocked completely and reversibly by atropine (5 microM) but not by propranolol (2.5 microM) and phentolamine (2.5 microM) administered together. When acetylcholine (1.0 or 0.05 microM) was infused on a background of choline stimulation, a small additional secretory response was elicited whenever the choline stimulus was submaximal, and, regardless of the choline concentration employed, addition of acetylcholine always induced tachyphylaxis. The results suggest that choline and acetylcholine act on the same population of muscarinic receptors, but it is unclear why choline does not evoke tachyphylaxis. The response to choline allows us to exclude a number of the possible causes of tachyphylaxis that have previously been considered, so that an excessive buildup of cytosolic free Ca now remains as the most likely cause of the phenomenon.

Acetylcholine↗

Dissociation of fluid secretion and energy supply in rat mandibular gland by high dose of ACh.

The effects of a high dose of acetylcholine (ACh) on oxygen consumption (VO2) and changes in phosphorus energy metabolites during secretion were studied in isolated perfused mandibular gland of rats at 24 degrees C. Sugar phosphates (SP), Pi, phosphocreatine (PCr), and ATP were identified by phosphorus-31 nuclear magnetic resonance spectroscopy. One micromole ACh induced a tachyphylactic secretory response, a persistently elevated VO2, and decreased PCr and ATP; 1 mM ACh caused an initial burst of secretion that was followed by suppression of secretion and a rapid increase in the VO2 to the same level as that with 1 microM ACh. These findings indicate a dissociation between secretion and VO2. During stimulation with 1 mM ACh, the level of PCr first decreased and then partially recovered, but the level of ATP continued to decrease and the levels of Pi and SP increased markedly. These findings suggest compartmentalization of creatine phosphokinase (CPK) systems and the possibility that a high concentration of ACh interferes with the transport of PCr between one CPK system near adenosinetriphosphatase and another system near mitochondria in acinar cells.

Acetylcholine↗

Ionic distribution in dopamine-stimulated NaCl fluid-secreting cockroach salivary glands.

The compound, racemose, innervated salivary glands of the cockroach Periplaneta americana closely resemble in structure and function the mammalian salivary glands (C.R. House, Biol. Rev. 55: 417-473, 1980). The quantitative distribution of Na, K, Cl, Ca, Mg, P, and S was investigated in the P-cells secreting isotonic NaCl and in duct lumens by using electron probe X-ray microanalysis of frozen-hydrated and frozen-dried cryosections. In the unstimulated glands in vitro the cells had (mmol/l cell-H2O) Na, 10; K, 110; Cl, 39 while the primary saliva had Na, 153; K, 4; Cl, 151. With 1 mumol dopamine in the bathing Ringer solution the P-cells had Na, 25; K, 177; Cl, 58 and the primary saliva, Na, 153; K, 26; Cl, 172. During passage through the ducts, the primary saliva was modified by an absorption of NaCl: more in unstimulated than in stimulated glands. It is proposed that the cells have a Na-K-ATPase both in the apical and basal cell membrane, as in vertebrate choroid plexus, and dopamine might increase the K and Na conductance of the basal cell membrane.

Animals↗

The chronically reserpinized rat as a model for cystic fibrosis: abnormal Cl- transport as the basis for reduced salivary fluid secretion.

Saliva secretion induced by 10(-6) M acetylcholine was reduced 74% in isolated, perfused submandibular glands of control rats when the gland was perfused with solutions containing either furosemide (10(-3) M) or sulfate (instead of chloride) as the major anion. In regular (Cl-containing) perfusates without furosemide, saliva secretion was reduced 74% in isolated glands of rats treated with seven intraperitoneal doses of reserpine (0.5 mg/kg body weight). In the latter, addition of furosemide or replacement of perfusate Cl- with SO = 4 caused a further 35% drop in saliva volumes. Salivary Cl- concentrations were lower in saliva from the treated animals and were reduced further by furosemide, which also reduced the Cl- concentrations of control saliva. In submandibular acini isolated from control glands, acute exposure to 36Cl (1 mu Ci/ml) resulted in a rapid uptake of tracer so that a constant content of isotope (approximately 9.5 nM/mg protein) was attained in 4-5 min and maintained for 30 min. This basal uptake reached 8.4 nM/mg protein in acini isolated from glands of reserpine-treated rats and attainment of a steady state of tracer content was delayed and required 8-10 min. Exposure to acetylcholine reduced uptake and steady state tracer content by 35% in control acini, but had no effect in acini of reserpine-treated rats. Acetylcholine caused a rapid decrease (42% in 1 min) in 36Cl content of control acini which were preloaded with tracer for 12 min, but only a 23% decrease in acini of reserpine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

The location and mechanism of hyperosmotic fluid secretion in the rectum of the saline-water mosquito larvae Aedes taeniorhynchus.

1. Ligation between the anterior and posterior segments of the rectum in vitro was used to demonstrate that the posterior rectum is the site of hyperosmotic secretion to the lumen side. Observations were consistent with a reabsorptive function for the anterior rectum. These results support predictions from ultrastructural studies of these two segments. 2. The initial potential of the rectal lumen, relative to the haemocoel side, was of opposite polarity in the anterior (-10 mV) and posterior (+ 10 mV) segments and these values decreased to -2 and +6 mV respectively in ligated recta which had secreted for 2 h. 3. A comparison of these potential difference measurements with concentration differences developed across the rectal epithelium under the same experimental conditions indicates that Na+, K+, Mg2+, and Cl- are all actively transported by the posterior segment to the lumen side. 4. The influence of different haemolymph concentrations of Na+, K+, and Cl- on the potential differences across the basal cell border and across the whole rectal epithelium are reported. Based on this and previous data, we propose a model for the organization of transport processes within the single celltype present in the posterior rectal epithelium.

Aedes↗