Active Cl Secretion Research Articles

Ion Transport Changes During Calcitonin-Induced Intestinal Secretion in Man

Previous studies have shown that synthetic salmon calcitonin (SCT) infused intravenously causes secretion of water and electrolytes in the jejunum of normal human subjects. The present experiments were carried out to learn more about the nature of this intestinal secretory process. During SCT- or synthetic human calcitonin (HCT)-induced intestinal secretion, the following observations were made: (1) There was no change in potential difference; (2) Cl was secreted against an electrochemical gradient; (3) unidirectional Na flux out of the lumen was decreased while the opposite flux was normal; (4) luminal pCO2 fell; (5) addition of glucose to the jejunal contents stimulated Na abdsorption, and this in turn counteracted the secretory effect of calcitonin. These findings suggest that calcitonin induces active Cl secretion and inhibits active Na absorption, and that HCO3 absorption is reduced by virtue of OH secretion; furthermore, jejunal glucose absorption and glucose-stimulated Na absorption are intact during calcitonin-induced secretion. Intravenous infusion of HCT caused intestinal secretion only when blood levels were much higher than occur physiologically; therefore, calcitonin is probably not a mediator of spontaneous variations of intestinal transport in normal people. However, because calcitonin induces secretion in the ileum as well as in the jejunum, hypercalcitonemia (within the range commonly found in patients with medullary carcinoma of the thyroid) could be a cause of severe secretory diarrhea.

Effect of staphylococcal enterotoxins A, B, and C, on ion transport and permeability across the flounder intestine.

SummaryPurified staphylococcal enterotoxins A, B, and C added to the mucosal and serosal bathing solution of winter flounder intestine in vitro caused changes in ion fluxes and electrical properties. An increase in Na and Cl fluxes was observed after the addition of these enterotoxins, with the greatest increase being in the serosal to mucosal flux for each ion resulting in an upward movement of both PD and Isc. In the staphylococcal enterotoxin treated intestine, the membrane permeability to small solute such as urea and thiourea did not increase significantly. The tissue resistance and the residual flux (JRnet) did not change significantly after adding the enterotoxins, suggesting that staphylococcal enterotoxins increase PD and Isc by stimulating active Na and Cl secretion via an electrogenic mechanism.

Ion Transport Across Isolated Ileal Mucosa Invaded by Salmonella

Abstract The effects of two different invasive strains (TML and SL 1027) of Salmonella tryphimurium on Na and Cl transport in the absence of an electrochemical gradient were measured across rabbit ileal mucosa in vitro. Only strain TML elicits ileal fluid secretion in vivo. Net Na transport is negligible and net Cl secretion occurs across mucosae invaded by TML. In contrast, mucosae invaded by SL 1027 show absorption of both Na and Cl, as occurs in normal ileum. The luminal addition of glucose stimulates Na absorption without affecting Cl transport across ileum invaded by either strain. Theophylline stimulates Na transport across TML-invaded mucosa, causing net secretion, and enhances Cl secretion. Across SL 1027-invaded tissues, theophylline reverses spontaneous ion absorption, causing secretion of both Na and Cl. The data suggest that stimulation of active Cl secretion combined with inhibition of spontaneous Na absorption may account for the diarrhea of salmonella enteritis. However, invasion of the mucosa alone by S. typhimurium is not necessarily associated with major alterations in ion transport, suggesting that a factor, in addition to invasion, is necessary for fluid secretion. The effects of theophylline are compatible with strain TML exerting submaximal stimulation of cyclic adenosine monophosphate activity or involving another metabolic pathway which also inhibits spontaneous Na absorption and stimulates Cl secretion.

Ion and Water Balance in the Ixodid Tick Dermacentor Andersoni

ABSTRACT The salivary gland of the ixodid tick, Dermacentor andersoni, can be induced to secrete fluid for at least 6 h when bathed in an artificial medium in vitro. Fluid secretion appears to be a consequence of active Cl secretion since (a) it is inhibited by 95 % when nitrate and by 100% when acetate replaces Cl in the bathing medium ; however, bromide can support secretion as well as Cl, (b) the rates of fluid and Cl secretion are linearly related to the concentration of Cl in the medium; and (c) the S/H ratio for Cl is greater than unity at all concentrations despite a transacinar P.D. of 35 mV (lumen negative). Although (in the presence of Na) a low concentration of K in the bathing medium stimulates the rate of fluid secretion fivefold, higher concentrations of K inhibit fluid secretion. The latter is largely due to a direct effect of K ion and not simply to increased osmotic pressure or reduced Na concentration. Fluid secretion is completely inhibited by 10−6 M ouabain. On the basis of these observations we propose that fluid secretion may be dependent on a Na-K activated ‘pump ATPase ‘, which is somehow involved in cation secretion. The S/H ratios of Na and K are greater than unity at all medium concentrations. The saliva secreted in vitro is slightly hypo-osmotic to the bathing medium over a wide range of medium concentration (300–920 mOsm/1). We postulate that the primary saliva is iso- or hyper-osmotic to the bathing medium; the final elaborated saliva is probably rendered hypo-osmotic by a process of solute reabsorption somewhere between the acini and the orifice of the main salivary duct.

Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins.

The effects of several prostaglandins (PG) and a highly purified preparation of cholera enterotoxin (CT) on intestinal mucosal adenyl cyclase activity and the effect of CT on intestinal mucosal cyclic 3',5'-adenosine monophosphate concentration were determined in guinea pig and rabbit small intestine and were correlated with the effects of the same agents on ion transport. Adenyl cyclase activity, measured in a crude membrane fraction of the mucosa, was found at all levels of the small intestine with the highest activity per milligram protein in the duodenum. The prostaglandins, when added directly to the assay, increased adenyl cyclase activity; the greatest effect (2-fold increase) was obtained with PGE(1) (maximal effect at 0.03 mM) and PGE(2). The prostaglandins also increased short-circuit current (SCC) in isolated guinea pig ileal mucosa, with PGE(1) and PGE(2) again giving the greatest effects. The prior addition of theophylline (10 mM) reduced the subsequent SCC response to PGE(1) and vice versa. It was concluded, therefore, that the SCC response to PGE(1), like the response to theophylline, represented active Cl secretion. CT increased adenyl cyclase activity in guinea pig and rabbit ileal mucosa when preincubated with the mucosa from 1 to 2.5 hr in vitro or for 2.5 hr in vivo but not when added directly to the assay. The increments in activity caused by PGE(1) and NaF were the same in CT-treated and control mucosa. Cyclic 3',5'-AMP concentration in rabbit ileal mucosa was increased 3.5-fold after a 2 hr preincubation with CT in vitro. Phosphodiesterase activity in the crude membrane fraction of the mucosa was unaffected by either CT or PGE(1). A variety of other agents including insulin, glucagon, parathormone, thyroid-stimulating hormone, L-thyroxine, thyrocalcitonin, vasopressin, and epinephrine all failed to change adenyl cyclase activity. It is concluded that CT and certain prostaglandins produce small intestinal fluid secretion by increasing mucosal adenyl cyclase activity, thereby stimulating an active secretory process.

Studies on the mechanism of salt and water secretion from the lacrimal gland.

By stimulating the lacrimal gland of rabbit with pilocarpine, the tears were collected through the fistula inserted into the nasolacrimal duct, and the ionic composition was analysed with special reference to the rate of lacrimal flow, and the ionic concentrations in serum. The secretion potential wasalso measured with reference to the secretion of ions in tears. Results obtained are as follows:1. The osmolarity of tears is mainly produced by salts which are mainly composed of Na+ and Cl-and partly of K+and HCO3-and is kept almost con stant at a slightly higher level than that of serum, irrespective of the rate of tear flow. The concentrations of Nat HCO3-and Cl- in tears are all kept constant, irrespective of the rate of tear flow, while the K+concentration changes parallel to changes of the rate of tear flow.2. The concentrations of Na+and HCO3- in tears are approximately the same as that of the respective ion in serum even when the concentration in serum is changed by salt infusion, while K+ and Cl- concentrations are always higher in tears than in serum. The Cl- concentration in tears bears a linear relation with that in serum of which the regression coefficient is 1 and the intercept constant is about 25mEq. The pH of tears is approximately the same as the serum pH and is determined by HCO3- concentration and CO2 partial pressure which equilibrate with those in serum.3. The potential being measured by external leading from the luminal side and the outside of the lacrimal gland, a resting potential of about 4-27mV was detected. The negative side of the potential is in the lumen of gland. The negativity of the potential in the luminal side increases as the rate of tear flow is increased by stimulation of lacrirnal gland, and thus the secretion potential of about 7-22mV appears. The secretion potential runs parallel to the time course of the rate of tear flow, though the peak of the former somewhat lags behind that of the latter.4. The increase of the resting potential as well as the secretion potential was provoked by raising the Cl concentration in serum by NaCl infusion. The changes of potential may be due to the acceleration of secretion. On the other hand, the potential was reduced after KCl infusion, probably owing to the promotion of K+ secretion by a rise of serum K+ concentration.5. From the above results and analysis of the interrelation between the rate of tear flow and the rate of ionic secretion as well as the secretion potential, it was deduced that the secretion potential as well as the water secretion (tear flow) of the lacrimal gland is associated with the active secretion of Cl- through the lacrimal gland cells, while Nat HCO3- are all transported passively in equilibration with those in serum. The K+ secretion is also an active process and affects the secretion potential to decrease.