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H J Binder

Publications and source records attributed to H J Binder.

At least 91 records · Page 5Linked to original sources
PubMed1985

Role of aldosterone and dietary potassium in potassium adaptation in the distal colon of the rat.

The present experiments were designed to differentiate the effects of aldosterone and chronic potassium loading in the mechanism of colonic potassium adaptation, using a recently described animal model that permits systematic manipulation of aldosterone and dietary potassium. Unidirectional 42K fluxes were performed under short-circuit conditions across isolated distal colonic mucosa from rats with intact adrenal glands and in adrenalectomized, hormone-replaced animals. Administration of a potassium-enriched diet reversed net potassium absorption (+0.43 +/- 0.10 muEq/h.cm2) in intact animals to net potassium secretion (-0.76 +/- 0.08 muEq/h.cm2). Infusion of aldosterone in adrenalectomized animals, in an amount equivalent to that produced by potassium loading in intact rats, reduced JnetK to zero (-0.03 +/- 0.06 muEq/h.cm2). Similarly, zero net potassium transport (-0.14 +/- 0.08 muEq/h.cm2) was observed when experimental rats were fed a potassium-enriched diet and maintained with basal aldosterone levels. Therefore, both elevated aldosterone levels and a potassium-enriched diet had an effect on net potassium transport, but neither produced the full effects of chronic potassium loading. An increase in net potassium secretion (-0.57 +/- 0.07 myEq/h.cm2) comparable to that of intact potassium-loaded animals did, however, occur when potassium loading and elevated aldosterone levels were combined in experimental animals. These studies demonstrate that (a) chronic potassium loading alters active potassium transport by an aldosterone-independent mechanism and (b) the mechanism of chronic potassium adaptation represents the additive effects of increased dietary potassium and aldosterone.

Adaptation, Physiological↗
PubMed1985

Evidence that aldosterone influences transport in target tissues by dissimilar mechanisms.

The present study was performed to answer the question: Is the action of aldosterone on electrolyte transport and electrical properties similar in all target tissues? Studies were performed in vivo in control animals and rats with secondary hyperaldosteronism, caused by a sodium-free diet, to compare the effects of hyperaldosteronism on distal colon with hormone-induced changes in proximal colon. In distal colon aldosterone increased net sodium absorption and potassium secretion approximately threefold. Transmural potential difference increased from -15 +/- 2 to -83 +/- 3 mV (lumen negative) and ISC rose from 167 +/- 26 to 1,023 +/- 17 microA X cm-2. These aldosterone-induced responses were completely inhibited by 0.1 mM amiloride. In contrast, in proximal colon potential difference was unchanged or increased slightly in experimental animals and ISC increased only 28% above control, although increases in net sodium and potassium transport were similar to changes observed in distal colon. Amiloride did not reduce sodium absorption in proximal colon of animals with hyperaldosteronism; ISC was decreased by 43%. These studies demonstrate that rat proximal colon is an aldosterone-sensitive tissue, but that the mechanism by which aldosterone influences sodium transport is not identical in distal and proximal portions of colon.

Aldosterone↗
PubMed1984

Effect of chronic hyperaldosteronism on the electrophysiology of rat distal colon.

Microelectrodes have been used to study the effects of aldosterone on the barriers and forces controlling sodium and potassium transport in rat distal colon. Compared to control tissues, hyperaldosteronism induced by dietary sodium depletion resulted in a 7-fold increase in transepithelial voltage (VT) and a 52% decrease in total resistance (RT). Increased VT reflected both a rise in the basolateral membrane voltage (Vbl) and a fall in the apical membrane voltage (VA). RT was resolved into its separate membrane components using nystatin (585 U X ml-1), and the decrease in RT produced by aldosterone was found to be due entirely to a 66% decrease in the apical membrane resistance (RA). Amiloride had no effect on the control tissues, but restored VT, Vbl and VA in tissues from sodium deprived animals to control values. Amiloride also increased RT in the experimental tissue, but the post-amiloride values remained significantly lower than those in controls. These results indicate, therefore, that hyperaldosteronism results in an increase in VT by hyperpolarizing the basolateral membrane, as well as depolarizing apical membrane in rat distal colon. The fall in RT, however, is due only to a fall in RA since Rbl and junctional resistance (Rj) were unaffected. The data are consistent with the concept that aldosterone acts to stimulate sodium absorption by increasing the rate of cell entry of sodium, through the induction of amiloride-sensitive sodium channels in the apical membrane, and enhances the rate of potassium secretion by increasing the electrical driving force towards the mucosal solution.

Amiloride↗
PubMed1984

Oxalate absorption and postprandial urine supersaturation in an experimental human model of absorptive hypercalciuria.

The effect of 1.25-dihydroxyvitamin D [1,25-(OH)2D] on dietary oxalate absorption and postprandial urine supersaturation with calcium oxalate was determined in 11 normal subjects. 1,25-(OH)2D increased the urinary excretion of orally administered [14C]oxalate in the 8 h period after a liquid meal containing 1.875 mmol of calcium and 0.83 mmol of oxalate (P less than 0.01), and during a 48 h period when the subjects ingested a diet containing 25 mmol of calcium and 3.3 mmol of oxalate/day (P less than 0.01); however, 1,25-(OH)2D administration had no effect on [14C]oxalate excretion when calcium was removed from the liquid meal. 1.25-(OH)2D increased 24 h urinary oxalate excretion from 28.7 +/- 2.1 mmol/mol of creatinine to 36.8 +/- 2.6 mmol/mol of creatinine (P less than 0.05) on the 10 mmol/day calcium diet and from 26.4 +/- 2.9 to 33.2 +/- 2.2 mmol/mol of creatinine (P less than 0.1) on the 25 mmol/day calcium diet. A linear correlation (r = 0.72) was found between plasma 1,25-(OH)2D levels and urinary [14C]oxalate excretion after the liquid meal. 1,25-(OH)2D administration produced postprandial supersaturation of urine with calcium oxalate and calcium oxalate crystalluria. These studies suggest that 1,25-(OH)2D increases oxalate absorption (and urinary excretion) by increasing calcium absorption, which results in less binding of calcium to oxalate in the intestine; therefore more oxalate is available for absorption. The combined effect of increased calcium and oxalate absorption results in postprandial supersaturation of urine with calcium oxalate, with resultant crystalluria.

Adult↗
PubMed1984

Mechanism of active potassium absorption and secretion in the rat colon.

To characterize and contrast the active potassium absorptive and secretory processes present in the rat colon, unidirectional 42K fluxes were performed under short-circuit conditions across isolated distal (D) and proximal (P) colonic mucosa of control rats and animals with hyperaldosteronism due to sodium depletion (aldosterone group). In the control D colon there was net potassium absorption (+0.51 +/- 0.07 mueq X h-1 X cm-2). The absorptive process appears electroneutral because net potassium flux ( JK net ) was unchanged in sodium-free Ringer solution (+0.76 +/- 0.12 mueq X h-1 X cm-2), whereas short-circuit current (Isc) was reduced to zero, and in chloride-free Ringer solution. In P colon of controls, net potassium secretion was -0.19 +/- 0.02 mueq X h-1 X cm-2 and was abolished by removal of sodium but not by removal of chloride. In both P and D colon aldosterone produced active potassium secretion (-0.39 +/- 0.06 mueq X h-1 X cm-2, P less than 0.001, and -0.90 +/- 0.07 mueq X h-1 X cm-2, P less than 0.001, respectively) that was sodium and chloride dependent. Although mucosal amiloride in D colon of aldosterone animals reduced net sodium flux to zero and reversed Isc from 4.1 +/- 0.6 to -1.1 +/- 0.1 mueq X h-1 X cm-2, net potassium secretion was not affected. Thus, in the presence of amiloride, Isc is accounted for by JK net (-0.93 +/- 0.12 mueq X h-1 X cm-2). These data indicate that 1) the active potassium absorptive process is electroneutral and could be explained by a potassium-proton exchange, and 2) the potassium secretory process is stimulated by aldosterone, is not inhibited by amiloride, and probably is electrogenic.

Aldosterone↗
PubMed1984

Role of opiate receptors in regulation of enkephalin stimulation of active sodium and chloride absorption.

The mechanism of opioid peptide stimulation of active Na and Cl absorption in rabbit ileum is not known. Since vasoactive intestinal peptide (VIP) modulation of electrolyte transport is mediated by specific membrane receptors, these experiments sought to determine whether membrane receptors for opioid peptides are present on rabbit ileal enterocytes. Although we found specific binding both of radiolabeled opioid peptides to homogenates of cerebrum and ileal myenteric plexi and of 125I-VIP to ileal enterocytes, specific binding of radiolabeled opioid peptides to either ileal enterocytes or their homogenates was not identified. In parallel studies, tetrodotoxin, an inhibitor of neurotransmission, did not alter VIP-stimulation of Cl secretion but inhibited D-Ala2-methionine-enkephalinamide-induced electrolyte absorption. These studies suggest that opioid peptide stimulation of active Na and Cl absorption is mediated by an unidentified intermediary agonist.

Absorption↗
PubMed1984

Apical membrane properties and amiloride binding kinetics of the human descending colon.

The apical membrane properties of the isolated human descending colon were characterized by use of current fluctuation analysis methods and microelectrode techniques. The Na+ channel blocker amiloride was used to evaluate apical membrane conductance and the transepithelial short-circuit current (Isc). Amiloride significantly reduced Isc and increased the membrane resistance ratio. At submaximal doses of amiloride in the mucosal bathing solution, fluctuation analysis of the Isc revealed a Lorentzian component in the power-density spectra. The dose-response relationship between amiloride and current noise parameters was consistent with a two-state mechanism of blocker interaction with the channel. The on and off rate constants for the blocker-receptor reactions, the single-channel currents, and the Na+ channel density were estimated and were similar to those from Na+ channels from other so-called tight epithelia. In addition, these studies revealed an amiloride-insensitive conductance in the apical membrane in parallel to the amiloride-blockable Na+ channels. This conductance may be due to potassium ions. If so, the apical membrane properties of the human descending colon may closely resemble those of the rabbit descending colon and rat distal colon.

Adult↗
PubMed1984

Serotonin-induced alteration of colonic electrolyte transport in the rat.

Serotonin, a calcium-dependent intestinal secretagogue, inhibits sodium chloride absorption in the rabbit ileum, but unlike cyclic adenosine monophosphate-dependent secretagogues, does not stimulate chloride secretion. Because bethanechol, a muscarinic cholinergic agonist that acts as a calcium-dependent, noncyclic adenosine monophosphate-mediated secretagogue, both inhibits sodium chloride absorption and stimulates active chloride secretion in the rat colon, experiments were performed with serotonin to determine the effect of serotonin on colonic ion transport. In luminal perfusion studies, intravenous infusion of serotonin significantly decreased net water and net sodium transport. In in vitro studies of sodium and chloride transport performed under short circuit conditions, serotonin decreased both net sodium and net chloride absorption and increased short circuit current (1.7 +/- 0.4, 4.0 +/- 0.6, and 2.3 +/- 0.3 mu Eq/h X cm2, respectively). The decrease in net chloride transport was significantly greater than that in net sodium absorption and the difference between these changes was equivalent to the change in short circuit current. Removal of serosal calcium inhibited all of the effects of serotonin on electrolyte transport. Tetrodotoxin, an inhibitor of neurotransmission, had no effect on serotonin-induced changes in electrolyte transport. These results demonstrate that serotonin both inhibits neutral sodium chloride absorption and stimulates active chloride secretion by a calcium-dependent process in the rat colon.

Animals↗
PubMed1983

Effect of tetrodotoxin on cholinergic agonist-mediated colonic electrolyte transport.

Muscarinic cholinergic agonists stimulate electrolyte secretion in the intestine; nicotinic agonists augment absorption. Recent studies in rabbit ileum suggest that nicotinic but not muscarinic agonists act via an intermediary neurotransmitter. These in vitro studies in rat colon were performed to determine whether tetrodotoxin (TTX), a potent neurotoxin, inhibits cholinergic agonist-induced changes in electrolyte transport. TTX did not significantly alter basal ion transport or the ion transport changes produced by either theophylline or bethanechol, a muscarinic agonist. At a concentration of 1 mM carbachol, a mixed muscarinic-nicotinic agonist, had no apparent effect on ion transport but in the presence of TTX significantly decreased net sodium absorption, similar to the effect produced by 1 microM carbachol alone. These results are consistent with the concept that in low concentrations carbachol acts predominantly as a muscarinic agonist; in high concentrations carbachol exhibits both muscarinic and nicotinic properties that are equivalent. We conclude that muscarinic agonists alter electrolyte transport by acting directly on the enterocyte and that nicotinic agonists act indirectly by stimulating the release of an intermediary neurotransmitter.

Animals↗
PubMed1983

Role of calcium in the regulation of colonic secretion in the rat.

In vitro experiments were performed in rat colon to define the role of calcium in the regulation of electrolyte transport. Neither basal net sodium absorption (JNanet) nor JClnet was affected by varying serosal calcium from 0 to 3.0 mM, but both were decreased by 4.8 mM calcium. Removal of serosal calcium completely inhibited the effect of bethanechol, a muscarinic cholinergic agonist, which inhibits neutral sodium-chloride absorption in 1.2 mM calcium. In contrast, theophylline significantly decreased JNanet and JClnet both in the presence and absence of calcium, but the effects of theophylline were significantly less in calcium-free media. In 3.0 mM calcium bethanechol inhibited JCLnet significantly greater than JNanet and in 4.8 mM calcium bethanechol decreased JClnet equivalent to the increase in short-circuit current without significantly altering JNanet. We conclude that 1) high [Ca2+] inhibits net sodium and net chloride absorption; 2) the alteration of electrolyte transport by bethanechol is dependent on extracellular calcium, and the alteration of electrolyte transport by theophylline is not dependent on extracellular calcium but may be dependent on intracellular calcium; and 3) in addition to inhibition of neutral NaCl absorption, bethanechol stimulates chloride secretion.

Animals↗
PubMed1983

Corticosteroid alteration of active electrolyte transport in rat distal colon.

To determine the effect of corticosteroids on active transport processes, unidirectional fluxes of 22Na, 36Cl, and 42K were measured under short-circuit conditions across isolated stripped distal colonic mucosa of the rat in control, secondary hyperaldosterone, and dexamethasone-treated animals. In controls net sodium and chloride fluxes (JNanet and JClnet) and short-circuit current (Isc) were 6.6 +/- 2.2, 7.6 +/- 1.6, and 1.3 +/- 0.2 mu eq X h-1 X cm-2, respectively. Although aldosterone increased Isc to 7.3 +/- 0.5 mu eq X h-1 X cm-2, JNanet (6.9 +/- 0.7 mu eq X h-1 X cm-2) was not altered and JClnet was reduced to 0 compared with controls. Dexamethasone also stimulated Isc but did not inhibit JClnet. In Cl-free Ringer both aldosterone and dexamethasone produced significant and equal increases in JNanet and Isc. Theophylline abolished JNanet in control animals but not in the aldosterone group. Aldosterone reversed net potassium absorption (0.58 +/- 0.11 mu eq X h-1 X cm-2) to net potassium secretion (-0.94 +/- 0.08 mu eq X h-1 X cm-2). Dexamethasone reduced net potassium movement to 0 (-0.04 +/- 0.12 mu eq X h-1 X cm-2). These studies demonstrate that 1) corticosteroids stimulate electrogenic sodium absorption and 2) aldosterone, but not dexamethasone, inhibits neutral NaCl absorption and stimulates active potassium secretion. The effects of mineralocorticoids and glucocorticoids on electrolyte transport are not identical and may be mediated by separate and distinct mechanisms.

Aldosterone↗
PubMed1983

Preferential binding of vasoactive intestinal polypeptide to basolateral membrane of rat and rabbit enterocytes.

Binding of radioiodinated vasoactive intestinal polypeptide (VIP) to intestinal cell membranes of the rabbit ileum and rat jejunum was investigated. Specific binding of 125I-labeled VIP could be demonstrated only on the basolateral membrane and not on the brush border membrane. This corresponded with the lack of an effect on ion transport when VIP was applied to the mucosal side of an in vitro preparation of rabbit ileum. VIP altered ion transport only when it was applied to the serosal side. The binding of 125I-VIP was specific and dependent upon incubation temperature. There was a close correlation between the potency of VIP for inhibition of 125I-VIP binding and that for increasing adenylate cyclase activity. These observations demonstrate that VIP receptors are located on the basolateral membrane.

Adenylyl Cyclases↗
PubMed1983

Cyclic adenosine monophosphate stimulates active potassium secretion in the rat colon.

To determine whether cyclic adenosine monophosphate influences active potassium transport in the rat colon, we studied the effect of dibutyryl cyclic adenosine monophosphate and theophylline on unidirectional transmural 42K fluxes across proximal colonic mucosa under short-circuited conditions. Active potassium secretion (-0.19 +/- 0.02 microEq/h X cm2) was present in animals maintained on a normal potassium diet. Both 0.5 mM dibutyryl cyclic adenosine monophosphate and 5 mM theophylline significantly increased net potassium secretion by 0.49 +/- 0.04 and 0.33 +/- 0.03 microEq/h X cm2, p less than 0.001, respectively; the stimulation of net potassium secretion was secondary to an increase in serosal-to-mucosal potassium transport without change in mucosal-to-serosal potassium movement. A similar increase in active potassium secretion (from -0.15 +/- 0.03 to -0.32 +/- 0.03 microEq/h X cm2, p less than 0.005) was produced by bethanechol, a cholinergic muscarinic agonist that alters sodium and chloride transport by a noncyclic adenosine monophosphate, calcium-dependent process. In animals maintained on a high potassium diet, active potassium secretion was significantly increased to -0.79 +/- 0.17 microEq/h X cm2 (p less than 0.001). In these potassium-loaded animals, theophylline produced a greater increase in active potassium secretion (0.91 +/- 0.10 vs. 0.33 +/- 0.03 microEq/h X cm2, p less than 0.001) than in animals fed a normal potassium diet. These studies demonstrate that cyclic adenosine monophosphate and noncyclic adenosine monophosphate mediated secretogogues stimulate active potassium secretion. We speculate that the mechanism by which cyclic adenosine monophosphate increases active potassium secretion is related to an increase in luminal potassium conductance.

Animals↗
PubMed1982

Increased risk of nephrolithiasis in patients with steatorrhea.

Patients with ileal disease have increased absorption of dietary oxalate, hyperoxaluria, and an increased incidence of nephrolithiasis. Patients with steatorrhea of varying etiologies also have hyperoxaluria. To determine whether steatorrhea per se is associated with nephrolithiasis, we reviewed the charts of all adult patients who had a 72-hr fecal fat analysis from 1968 to 1978. The 159 patients with steatorrhea were compared to 162 patients without steatorrhea. The two groups were comparable in age, sex, urine specific gravity, and serum uric acid and phosphorus; serum calcium was slightly less in the steatorrhea group (8.7 +/- 0.1 vs 9.0 +/- 0.1, P less than 0.02). Although 19 patients with steatorrhea had nephrolithiasis compared to 7 control patients (P = 0.01), 15 of these 19 patients had ileal disease and only 4 of the 118 patients with steatorrhea but without ileal disease had stones. Categorical data analysis revealed that steatorrhea, diarrhea (stool weight greater than 225 g/day), male sex, and ileal disease were significantly associated with nephrolithiasis with a relative risk of 3.0, 2.7, 3.1, and 8.0, respectively. When patients without ileal disease were analyzed separately, however, steatorrhea, diarrhea, and sex were no longer risk factors. In contrast, in patients with ileal disease the incidence of nephrolithiasis increased with the severity of steatorrhea. The relative risk of nephrolithiasis in male patients with ileal disease and fecal fat greater than 20 g/day was 26.3 (P less than 0.01). Thus, the presence of both ileal disease and steatorrhea greatly increases the risk of nephrolithiasis; however, neither steatorrhea alone nor ileal disease alone are risk factors for nephrolithiasis.

Celiac Disease↗
PubMed1982

Mechanism of cholinergic regulation of electrolyte transport in rat colon in vitro.

Cholinergic agonists inhibit sodium and chloride absorption in the intestine and often produce secretion. To determine the mechanism of cholinergic regulation of intestinal electrolyte transport, the effects of bethanechol on ion transport were studied in the rat colon in vitro. The addition of 1 mM bethanechol produced an initially large but short-lived increase in short-circuit current (Isc) (171 +/- 19 microA/cm2). Bethanechol decreased net sodium and net chloride absorption (2.5 +/- 0.5 and 2.9 +/- 0.9 mueq . h-1 . cm-2, respectively) and increased Isc (0.8 +/- 0.3 mueq . h-1 . cm-2) during the steady-state period. All these effects were inhibited by 1 microM atropine, which alone had no effect on ion transport. The removal of either sodium or chloride also inhibited the effect of bethanechol. cAMP content did not increase in isolated enterocytes incubated with bethanechol; however, calcium removal from the serosal bathing solution inhibited the bethanechol-induced changes in ion transport. These results indicate that cholinergic muscarinic agonists alter sodium and chloride transport in the colon by inhibiting coupled NaCl absorption by a calcium-dependent, non-cAMP-mediated process.

Animals↗
PubMed1982

Demonstration of net potassium absorption in mammalian colon.

The present in vivo studies were performed in the rat to determine whether the colon was capable of net potassium absorption, as well as secretion, and to further elucidate the process responsible for net potassium movement. Both the proximal and distal lumina of the colon of control, potassium-deficient, and potassium-loaded animals were perfused with solutions containing either 140 or 20 mmol/l sodium. Net potassium secretion was present in both proximal and distal colon of control animals during perfusion with the 140 mmol/l sodium solution. The rate of net potassium secretion was reduced in the potassium-deficient animals. During perfusion with the 20 mmol/l sodium solution, the rate of potassium secretion was also reduced (compared with control perfusion solution) in both the control and potassium-deficient animals. As a result, there was net potassium absorption (0.94 +/- 0.14 mueq.1-1.g dry wt-1) and zero net potassium movement in the distal and proximal segments, respectively, of the potassium-deficient animals perfused with the low-sodium solution. Additional studies were performed to determine whether net potassium secretion was saturable and showed that, during progressive increases in the plasma potassium level, net secretion was constant at plasma potassium levels above 11-13 meq/l. These data, therefore, demonstrate that the mammalian colon regulates intestinal transport of potassium by both absorptive and secretory mechanisms and that a carrier-mediated process probably regulates both transport processes.

Animals↗