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H J Binder

Publications and source records attributed to H J Binder.

At least 109 records · Page 6Linked to original sources
PubMed1982

Mechanism of potassium adaptation.

After chronic dietary potassium loading, epithelia in distal portions of the nephron and large intestine adapt to increase the rate of potassium secretion. This response to increased excretory loads of potassium maintains overall external balance and protects against the potentially lethal effects of hyperkalemia. The cellular adaptation in epithelia involved in preserving potassium homeostasis during potassium loading is characterized by an increase in the number of potassium pumps, reflected by an increase in Na-K-ATPase activity, in the basolateral cell membrane due, at least in part, to an amplification in the area of this membrane, and by an increase in transepithelial potential difference in most, but not all, adapted epithelia. These changes suggest that potassium adaptation is due to a step-up in the rate of cell uptake of potassium. In addition to chronic dietary loading, other conditions such as chronic renal insufficiency, elevated levels of mineralocorticoids, and administration of glucocorticoids are also characterized by accelerated rates of potassium secretion in the distal nephron and colonic mucosa and stimulation of Na-K-ATPase in basolateral portions of the cell membrane. These cellular changes in epithelia with increased capacity for potassium secretion are discussed in the context of our present understanding of mechanisms that control potassium excretion in urine and feces.

Adaptation, Physiological↗
PubMed1982

Muscarinic receptors on rat isolated colonic epithelial cells. A correlation between inhibition of [3H]quinuclidinyl benzilate binding and alteration in ion transport.

Muscarinic cholinergic agonists stimulate secretion or inhibit absorption in the large intestine both in vivo and in vitro, effects that are completely inhibited by atropine, a specific muscarinic antagonist. These studies were performed to determine if the muscarinic-induced alteration in electrolyte transport in rat colon was produced by muscarinic agonists binding directly to receptors on colonic enterocytes. We found that crude membranes prepared from rat isolated colonic epithelial cells had a specific, saturable, high affinity receptor for L-[benzilic-4,4-3H]quinuclidinyl benzilate, a potent muscarinic antagonist with an apparent dissociation coefficient of 0.56 +/- 0.11 nM and a maximum number of binding sites of 42.5 +/- 5.7 fmol/mg protein. Muscarinic antagonists inhibited L-[benzilic-4,4-3H]quinuclidinyl benzilate binding in nanomolar concentrations, and muscarinic agonists inhibited L-[benzilic-4,4-3H]quinuclidinyl benzilate binding in micromolar concentrations. In parallel studies, oxotremorine and bethanechol, muscarinic agonists, and racemic quinuclidinyl benzilate altered short-circuit current in rat colon in vitro in concentrations that were in good agreement with the concentrations that inhibited L-[benzilic-4,4-3H]quinuclidinyl benzilate binding to the crude membrane preparation. Thus, these studies demonstrate that the muscarinic-induced alteration in colonic electrolyte transport is directly related to agonist binding to a specific muscarinic receptor on the colonic epithelial cell.

Animals↗
PubMed1981

The effect of somatostatin and enkephalin on ion transport in the intestine.

SRIF and enkephalin stimulate net Na and C1 absorption in the rabbit ileum and appear to do so primarily by stimulating the coupled influx of Na and C1 across the brush border membrane. The stimulatory effect of enkephalin on ion transport is blocked by verapamil and Ca-free solution, indirectly indicating that enkephalin may work as a Ca-channel blocker. The resultant lowering in cytosolic calcium level stimulates Na and C1 absorption. SRIF was able to block the effect of cyclic AMP-dependent and cyclic AMP-independent secretogogues in the rat colon without affecting cyclic AMP levels suggesting that it is inhibiting a distal step in the secretory pathway, probably involving a final common pathway. SRIF infusion blocked diarrhea in a patient with the carcinoid syndrome, indicating that it may be therapeutically useful in the treatment of secretory diarrheas. The antidiarrheal effect of opiates is probably due in part to their effect on electrolyte absorption, rather than an effect solely on intestinal motility.

Animals↗
PubMed1981

Corticosteroid-binding studies in cytosol of colonic mucosa of the rat.

Cytosolic binding of [3H]dexamethasone was studied in the colon of the rat. [3H]dexamethasone binding was rapid and stable at 4 degrees C for 240 min. Scatchard analysis revealed a Kd of 6.2 +/- 0.5 X 10(-9) M and a binding capacity of 149 +/- 6.4 fmol/mg cytosolic protein (100,000-g fraction). Although dexamethasone inhibited [3H]dexamethasone binding more than that of aldosterone, [3H]aldosterone binding was inhibited equally by both aldosterone and dexamethasone. The relative order of potency of other steroids to inhibit [3H]dexamethasone binding was: dexamethasone greater than progesterone greater than spironolactone greater than aldosterone greater than corticosterone greater than cortexolone greater than estradiol. In other experiments, low doses of dexamethasone and aldosterone were infused into adrenalectomized animals to determine functional importance of these cytosolic steroid receptors. One-hour infusion of aldosterone at 2 micrograms/100 g body wt, which was the minimal dose of dexamethasone that increased transmural potential difference, did not alter the potential difference. These studies demonstrate the presence of a cytosolic receptor for dexamethasone and suggest that the action of dexamethasone on electrolyte transport in adrenalectomized animals is not mediated by the mineralocorticoid type of receptor and may be mediated by the specific high-affinity receptor for dexamethasone.

Aldosterone↗
PubMed1981

Demonstration of active potassium transport in the mammalian colon.

The mechanism responsible for K transport in the mammalian colon is controversial. Experiments were performed to determine whether K secretion involves active as well as passive driving forces in controls and in animals with a marked increase in K secretion. In these experiments a steady-state solution was established in proximal and distal colon of both control rats and animals fed a K-enriched diet during in vivo luminal perfusion, to compare the observed luminal [K] with predicted equilibrium [K] when net water and electrolyte movement approached zero. Transmural potential difference was measured simultaneously. A difference between the predicted equilibrium and observed luminal [K] under this condition indicates active transport. In controls the observed [K] of 20 mmol/liter in proximal colon markedly exceeded the predicted value of 6.2 +/- 0.3, mean +/- SE, indicating active secretion. In contrast, the observed [K] in distal colon of 5 mmol/liter was less than predicted (10.0 +/- 1.0), suggesting active absorption. In K-loaded animals active K secretion was demonstrable and increase above control in both segments of colon. In proximal colon the observed [K] rose to 40 mmol/liter, compared to a predicted value of 7.2 +/- 0.3, whereas in distal colon the observed [K] was 50 mmol/liter vs. a predicted value of 7.0 +/- 0.8. These studies suggest active K secretion in proximal, but not in distal colon of control animals. Further, these data suggest that the increase in the capacity for K secretion that occurs in response to chronic K loading involves stimulation of an active mechanism in both proximal and distal colon.

Animals↗
PubMed1980

Effect of prostaglandin on ion transport across isolated colonic mucosa.

The effect of prostaglandins (PG) on colonic ion transport was investigated in in vitro experiments in the rat. Both PGE1 and PGA1 increased short-circuit current (Isc), potential difference, and mucosal cyclic AMP levels, but PGE1 was more potent than PGA1. 10(-4) M PGE1 inhibited active sodium transport across short-circuited colonic mucosa (6.1-1.3 microEq/hr/cm2). This effect, coupled with an increase in Isc, is consistent with prostaglandin stimulation of active anion secretion and with the recent suggestions that prostaglandins may be important intermediaries in the process by which several laxatives alter large-intestinal fluid and electrolyte movement.

Animals↗
PubMed1980

Receptors for vasoactive intestinal peptide and secretin on small intestinal epithelial cells.

Binding of 125I-labeled vasoactive intestinal peptide (VIP) to dispersed enterocytes prepared from guinea pig small intestine was saturable, temperature dependent, and reversible, and reflected interaction of the labeled peptide with a single class of binding sites. Each enterocyte possessed approximately 60,000 binding sites and binding of the tracer to these sites could be inhibited by VIP [concentration for half-maximal effect (Kd), 12 nM] and by secretin (Kd greater than 1 micro M), but not by glucagon, gastrin, cholecystokinin, calcitonin, bombesin, litorin, physalaemin, substance P, eledoisin, serotonin, carbamylcholine, or histamine. With VIP and secretin, there was a close correlation between the relative potency for inhibition of binding of 125I-VIP and that for increasing cellular cAMP. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of cellular cAMP. In addition to inhibiting binding of 125I-VIP and increasing cellular cAMP in enterocytes, secretin caused an increase in short-circuit current across guinea pig small intestine in vitro. Prostaglandin E1 increased cellular cAMP, but did not alter binding of 125I-VIP and the increase in cAMP caused by prostaglandin E1 plus VIP or secretin was equal to the sum of the increase caused by each agent alone.

Animals↗
PubMed1980

Role of glucocorticoids and aldosterone in maintenance of colonic cation transport.

Adrenalectomized rats were maintained on physiologic replacement doses of aldosterone or dexamethasone for 24 h after adrenalectomy. Net cation movement and transmural potential difference were determined during in vivo perfusion of the colon. Adrenalectomy without replacement steroids resulted in marked reduction of sodium and water absorption, potassium secretion, and transmural potential difference (PD). Aldosterone 10 microgram . 100 g body wt-1 . 24 h-1 significantly increased net potassium secretion above adrenalectomized levels but did not restore transport to control levels. Sodium and water absorption and transmural PD were not affected. Aldosterone 30 microgram . 100 g body wt-1 . 24 h-1 increased but did not restore net movement of sodium or potassium to control levels. In contrast to aldosterone, physiologic amounts of dexamethasone, 10 microgram . 100 g body wt-1 . 24 h-1, preserved normal electrolyte movement and electrical properties in adrenalectomized rats. In additional experiments the aldosterone antagonist spironolactone was administered for 3 days to rats with intact adrenal function. Net sodium absorption fell only 22% below control with insigificant decreases in potassium secretion and transmural PD. These data suggest that glucocorticoid hormones exert regulatory control of basal colonic fluid and electrolyte function.

Adrenalectomy↗
PubMed1980

Mechanism of increased potassium secretion in potassium loading and sodium deprivation.

Chronic K loading and Na deficiency increase the capacity of colonic cells to secrete K and are characterized by increases in Na-K-ATPase activity and, as recently shown by our laboratory, the area of basolateral membrane. The present experiments were performed in rat colon to evaluate the quantitative and qualitative changes that occur in the enzymes after induction of K adaptation. Changes in specific binding of [3H]ouabain to a plasma membrane-rich fraction of colonic mucosal cells correlated directly with changes in enzyme activity. In Na-deficient animals the number of ouabain-binding sites increased from 63.6 in controls to 111.2 pmol/mg protein, while the KD for ouabain was unchanged. The Km for ATP was not altered in experimental animals, although Vmax rose twofold. Further studies showed no change in the activity of adenylate cyclase, a marker enzyme for basolateral membrane, in the plasma membrane-rich fraction from experimental cells, although Na-K-ATPase activity increased significantly. These data indicate that increased Na-K-ATPase activity in K-adapted colonic cells reflects an absolute increase in number of pump sites, due, at least in part, to an increase in area of basolateral cell membrane. In addition, in sodium-deprived animals the present data suggest an increase in the density of K pumps in basolateral cell membrane.

Adenylyl Cyclases↗
PubMed1980

Effect of D-alanine methionine enkephalin amide on ion transport in rabbit ileum.

The presence of enkephalins in the intestine and the use of opiates to treat diarrheal diseases suggests that enkephalins may affect intestinal ion transport. Using isolated rabbit ileal mucosa, we found that leucine enkephalin, methionine enkephalin, and D Ala2-methionine enkephalin amide (D Ala2-Met E) decreased the short circuit current (Isc) and potential difference although the effect of D Ala2-Met E was more pronounced and prolonged. D Ala2-Met E increased net sodium (+1.27 +/- 0.5 mu eq/cm2h), and chloride absorption (+2.33 +/- 0.4), and increased tissue conductance by 37%. Although the effect of enkaphalin on ion transport is opposite that of cyclic AMP, D-Ala2-Met had no effect on basal or vasoactive intestinal polypeptide-stimulated cyclic AMP levels. The effect of D-Ala2-Met E on Isc was blocked by naloxone, suggesting the involvement of specific opiate receptors. Tetrodotoxin completely blocked the decrease in Isc induced by D-Ala2-Met E but not by epinephrine, inferring that enkephalins are preganglionic neurotransmitters. The effect of D-Ala2-Met E on Isc was not blocked by phentolamine, haloperidol, or pretreatment of animals with 6-hydroxydopamine, suggesting that enkephalin does not affect the Isc by stimulating the release of alpha-adrenergic or dopaminergic agonists. D-Ala2-Met E also decreased the Isc in the presence of carbachol and bethanechol, indicating that enkephalin does not inhibit the release of acetylcholine. Further, up to 10 mu M atropine had no effect on the Isc. These studies demonstrate that enkephalins stimulate intestinal ion transport and may do so by stimulating (or inhibiting) the release of a nonadrenergic, noncholinergic neurotransmitter.

Animals↗
PubMed1980

Somatostatin stimulates sodium and chloride absorption in the rabbit ileum.

The effect of somatostatin on ion transport in the rabbit ileum was determined. Somatostatin (a) decreased that short circuit current (Isc) (-1.0 +/- 0.2 mueq/hr . cm2) and potential difference (PD), (b) increased net Na and Cl absorption (+1.5 +/- 0.3 and +2.4 +/- 0.4 mueq/hr . cm2, respectively), and (c) increased tissue conductance (+5.1 +/- 1.3 mmhos/cm2). The increase in net Na and Cl absorption was primarily due to an increase in mucosal-to-serosal movement of these ions. Somatostatin had no effect on 3-0-methyl-glucose absorption, nor the increase in Isc produced by either 3-0-methyl-glucose or glucose. Phentolamine did not reverse the decrease in Isc produced by somatostatin and catecholamine depletion with reserpine or 6-OH-dopamine did not inhibit the somatostatin-induced decrease in Isc. The cholinergic agonists, carbachol and bethanechol, and no effect on somatostatin-induced decrease in Isc and atropine neither affected Isc nor blocked the effect of somatastatin on Isc. These studies demonstrate that somatostatin increased both Na Na and Cl absorption across rabbit ileal mucosa and suggest that these effects do not involve adrenergic or cholinergic agonists. Somatostatin may have a direct effect on the enterocyte.

Animals↗
PubMed1979

Prolonged survival in chronic lymphocytic leukemia: a case report.

A patient with long-standing chronic lymphocytic leukemia with both humoral and cellular immunodeficiency had lymph node receptor evidence of a B lymphocyte disorder. He was also found to secrete the Epstein--Barr virus and, late in his illness, developed a markedly positive antinuclear antibody. Interrelationship of these findings may be important in the ultimate determination of the etiology and functional mechanisms in lymphocyte malignancies.

Adult↗
PubMed1979

Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat.

Perfusion of the colon with ricinoleic acid produces fluid and electrolyte accumulation. The mechanism of these changes in water and electrolyte movement is uknown. These studies were designed to determine whether ricinoleic acid effects active ion transport across isolated rat colonic mucosa. 0.5 mM Na ricinoleate produced significant increases in potential difference (3.8 +/- 0.5 mV) and short-circuit current (Isc) (99.2 +/- 10.1 muA/cm2). The increases in Isc produced by Na ricinoleate were inhibited by both removal of bicarbonate and chloride and by the presence of theophylline. The hydroxy fatty acid also resulted in a significant decrease in net Na absorption from 4.7 +/- 0.8 to 0.1 +/- 0.7 mueq/h cm2 and reversed net Cl transport from absorption (+ 4.5 +/- 0.9) to secretion (-2.2 +/- mueq/h cm2). In parallel studies 0.5 mM Na ricinoleate increased mucosal cyclic AMP content by 58%. The concentrations of Na ricinoleate required to produce detectable and maximal increases in both Isc and cyclic AMP were the same. These results provide evidence in support of the concept that hydroxy fatty acid-induced fluid and electrolyte accumulation is driven by an active ion secretory process.

Animals↗