Net Ion Transport Research Articles

Physiological and morphological effects of alendronate on rabbit esophageal epithelium

Alendronate, an aminobisphosphonate, produces as a side effect a topical (pill induced) esophagitis. To gain insight into this phenomenon, we assessed the effects of luminal alendronate on both esophageal epithelial structure and function. Sections of rabbit esophageal epithelium were exposed to luminal alendronate at neutral or acidic pH while mounted in Ussing chambers to monitor transmural electrical potential difference (PD), short-circuit current (I(sc)), and resistance (R). Morphological changes were sought by light microscopy in hematoxylin and eosin-stained sections. Impedance analysis was used for localization of alendronate-induced effects on ion transport. Luminal, but not serosal, alendronate (pH 6.9-7.2), increased PD and I(sc) in a dose- and time-dependent manner, with little change in R and mild edema of surface cell layers. The changes in I(sc) (and PD) were reversible with drug washout and could be prevented either by inhibition of Na,K-ATPase activity with serosal ouabain or by inhibition of apical Na channels with luminal acidification to pH 2.0 with HCl. An effect on apical Na channel activity was also supported by impedance analysis. Luminal alendronate at acidic pH was more damaging than either alendronate at neutral pH or acidic pH alone. These data suggest that alendronate stimulates net ion (Na) transport in esophageal epithelium by increasing apical membrane sodium channel activity and that this occurs with limited morphological change and no alteration in barrier function. Also alendronate is far more damaging at acidic than at neutral pH, suggesting its association with esophagitis requires gastric acid for expression. This expression may occur either by potentiation between the damaging effects of (refluxed) gastric acid and drug or by acid-induced conversion of the drug to a more toxic form.

Metal and Oxygen Ion Transport during Ionic Conduction in Amorphous Anodic Oxide Films

A mathematical model was developed for ionic conduction in amorphous oxide films. The model is based on a hypothesized “defect cluster” mechanism in which both metal and oxygen ions are involved in transport. Defect clusters are created by inward displacement of oxygen ions around an oxygen vacancy‐like defect in response to the vacancy's electric field. Metal ions are assumed to migrate easily in the gap between the first and second layer of oxygen ions around the vacancy. The model includes the polarization of the conductive gap in the applied electric field, the exchange of mobile metal ions in the cluster with stationary metal ions in the surrounding oxide, and space charge generated in the film by clusters and oxide nonstoichiometry. The rate‐limiting step is the jump of the oxygen vacancy in the cluster. It was found that polarization of the cluster leads to a stoichiometric excess of metal ions in the cluster and that this excess produces a net transport of metal ions due to the motion of the cluster. The metal ion transport number was found to increase with electric field and to depend on the dielectric constant and cluster size. The field dependence follows that found experimentally. The calculated transport numbers are in quantitative agreement with experimental values for tantalum, niobium, and tungsten oxide but smaller than experimental values for aluminum oxide. The field coefficient in the high‐field‐conduction‐rate expression is also predicted and agrees with experimental values to within 10%. © 1999 The Electrochemical Society. All rights reserved.

KGF prevents hyperoxia-induced reduction of active ion transport in alveolar epithelial cells.

We evaluated the effects of acute hyperoxic exposure on alveolar epithelial cell (AEC) active ion transport and on expression of Na+ pump (Na+-K+-ATPase) and rat epithelial Na+ channel subunits. Rat AEC were cultivated in minimal defined serum-free medium (MDSF) on polycarbonate filters. Beginning on day 5, confluent monolayers were exposed to either 95% air-5% CO2 (normoxia) or 95% O2-5% CO2 (hyperoxia) for 48 h. Transepithelial resistance (Rt) and short-circuit current (Isc) were determined before and after exposure. Na+ channel alpha-, beta-, and gamma-subunit and Na+-K+-ATPase alpha1- and beta1-subunit mRNA levels were quantified by Northern analysis. Na+ pump alpha1- and beta1-subunit protein abundance was quantified by Western blotting. After hyperoxic exposure, Isc across AEC monolayers decreased by approximately 60% at 48 h relative to monolayers maintained under normoxic conditions. Na+ channel beta-subunit mRNA expression was reduced by hyperoxia, whereas alpha- and gamma-subunit mRNA expression was unchanged. Na+ pump alpha1-subunit mRNA was unchanged, whereas beta1-subunit mRNA was decreased approximately 80% by hyperoxia in parallel with a reduction in beta1-subunit protein. Because keratinocyte growth factor (KGF) has recently been shown to upregulate AEC active ion transport and expression of Na+-K+-ATPase under normoxic conditions, we assessed the ability of KGF to prevent hyperoxia-induced changes in active ion transport by supplementing medium with KGF (10 ng/ml) from day 2. The presence of KGF prevented the effects of hyperoxia on ion transport (as measured by Isc) relative to normoxic controls. Levels of beta1 mRNA and protein were relatively preserved in monolayers maintained in MDSF and KGF compared with those cultivated in MDSF alone. These results indicate that AEC net active ion transport is decreased after 48 h of hyperoxia, likely as a result of a decrease in the number of functional Na+ pumps per cell. KGF largely prevents this decrease in active ion transport, at least in part, by preserving Na+ pump expression.

Enteropathogenic E. coli attenuates secretagogue-induced net intestinal ion transport but not Cl- secretion.

Enteric bacterial pathogens often increase intestinal Cl- secretion. Enteropathogenic Escherichia coli (EPEC) does not stimulate active ion secretion. In fact, EPEC infection decreases net ion transport in response to classic secretagogues. This has been presumed to reflect diminished Cl- secretion. The aim of this study was to investigate the influence of EPEC infection on specific intestinal epithelial ion transport processes. T84 cell monolayers infected with EPEC were used for these studies. EPEC infection significantly decreased short-circuit current (Isc) in response to carbachol and forskolin, yet 125I efflux studies revealed no difference in Cl- channel activity. There was also no alteration in basolateral K+ channel or Na+-K+-2Cl- cotransport activity. Furthermore, net 36Cl- flux was not decreased by EPEC. No alterations in either K+ or Na+ transport could be demonstrated. Instead, removal of basolateral bicarbonate from uninfected monolayers yielded an Isc response approximating that observed with EPEC infection, whereas bicarbonate removal from EPEC-infected monolayers further diminished Isc. These studies suggest that the reduction in stimulated Isc is not secondary to diminished Cl- secretion. Alternatively, bicarbonate-dependent transport processes appear to be perturbed.

Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis

Background & Aims: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis (UC) was performed. Methods: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy. Results: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 ± 5 to 20 ± 3 Ω · cm 2, which in conventional analysis is masked by an increase in subepithelial resistance from 14 ± 1 to 36 ± 3 Ω · cm 2 caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 ± 0.25 to 4.76 ± 0.47 at the surface and from 7.26 ± 0.31 to 5.46 ± 0.37 in the crypts. Conclusions: The inflamed colonic mucosa in UC has an impaired barrier function that is much more pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC. GASTROENTEROLOGY 1999;116:301-309

CD4+ T cells mediate superantigen-induced abnormalities in murine jejunal ion transport.

The immunomodulatory properties of bacterial superantigens (SAgs) have been defined, yet comparatively little is known of how SAgs may affect enteric physiology. Staphylococcus aureus enterotoxin B (SEB) was used to examine the ability of SAgs to alter epithelial ion transport. BALB/c mice, severe combined immunodeficient (SCID, lack T cells) mice, or SCID mice reconstituted with lymphocytes or CD4+ T cells received SEB intraperitoneally, and jejunal segments were examined in Ussing chambers; controls received saline only. Baseline short-circuit current (Isc, indicates net ion transport) and Isc responses evoked by electrical nerve stimulation, histamine, carbachol, or forskolin were recorded. Serum levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were measured. SEB-treated BALB/c mice showed elevated serum IL-2 and IFN-gamma levels, and jejunal segments displayed a time- and dose-dependent increase in baseline Isc compared with controls. Conversely, evoked ion secretion was selectively reduced in jejunum from SEB-treated mice. Elevated cytokine levels and changes in jejunal Isc were not observed in SEB-treated SCID mice. In contrast, SCID mice reconstituted with T cells were responsive to SEB challenge as shown by increased cytokine production and altered jejunal Isc responses that were similar to those observed in jejunum from SEB-treated BALB/c mice. We conclude that exposure to a model bacterial SAg causes distinct changes in epithelial physiology and that these events can be mediated by CD4+ T cells.

Reduction in net ion transport induced by enteropathogenic E. coli infection of intestinal epithelial cells is attributable to bicarbonate transport

Reduction in net ion transport induced by enteropathogenic E. coli infection of intestinal epithelial cells is attributable to bicarbonate transport

Superantigen activation of immune cells evokes epithelial (T84) transport and barrier abnormalities via IFN-gamma and TNF alpha: inhibition of increased permeability, but not diminished secretory responses by TGF-beta2.

Superantigens (SAgs) are extremely potent stimulants of T cell activity that have been implicated in the etiopathophysiology of inflammatory disease. Here, we tested the hypothesis that Staphylococcus aureus enterotoxin B (SEB), a model SAg, can alter epithelial transport and/or barrier functions via immune stimulation. Confluent monolayers of the human colonic T84 epithelial cell line, grown on filter supports, were cocultured with SEB +/- PBMC. Subsequently, T84 transport (consisting of baseline short-circuit current (Isc, indicates net ion transport) and secretory responses to carbachol and forskolin) and barrier functions (consisting of transepithelial resistance and fluxes of 3H-labeled mannitol and 51Cr-EDTA) were examined in Ussing chambers. T84 monolayers cocultured with SEB-activated PBMC displayed a time- and dose-dependent decrease in secretory responses to carbachol and forskolin and a significant increase in permeability. These dramatic changes in epithelial function were not due to reduced epithelial viability. Neutralizing Abs to IFN-gamma partially prevented the transport abnormalities, and Abs to TNF-alpha inhibited the increase in epithelial permeability. Abs to IL-1beta and IL-6 did not modulate the SEB-activated PBMC-induced T84 pathophysiology. Addition of TGF-beta2 to conditioned medium from SEB-activated PBMC partially inhibited the increase in T84 permeability but did not affect the transport abnormalities. We conclude that SAgs can elicit epithelial irregularities characteristic of enteric inflammation and that IFN-gamma and TNF-alpha are key mediators in this coculture model of epithelial dysfunction. Additionally, we would highlight the role that TGF-beta2 may play in preventing prolonged increases in epithelial permeability.

Sodium/proton antiporter in the euryhaline crab Carcinus maenas: molecular cloning, expression and tissue distribution.

Gill epithelial cells of euryhaline crustaceans demonstrate net inward transport of sodium ions, possibly via apical Na+/H+ antiporters, Na+/K+/2Cl- cotransporters or Na+ channels working in series with the basolateral Na(+) + K(+)-ATPase. We have identified and sequenced the cDNA coding for a crustacean Na+/H+ antiporter, starting with mRNA isolated from gills of the euryhaline green shore crab Carcinus maenas. The complete 2595-base-pair cDNA includes an open reading frame coding for a 673-amino-acid protein. A search of GenBank revealed more than 20 high-scoring matches, all Na+/H+ antiporter sequences from mammalian, amphibian, teleost and nematode species. Injection of Xenopus laevis oocytes with cRNA transcribed from the cloned crab sequence substantially enhanced Na(+)-dependent H+ efflux from the oocytes. Analysis of crab tissue antiporter mRNA levels by semi-quantitative reverse transcription-polymerase chain reaction revealed that posterior and anterior gills of Carcinus maenas expressed this antiporter the most strongly, followed in decreasing order by skeletal muscle, hepatopancreas, hypodermis and heart. Hydropathy and transmembrane alpha-helix analysis suggested a 10-helix membrane-spanning topology of the antiporter protein. It is clear from this study that Carcinus maenas gills vigorously transcribe a gene coding for a Na+/H+ antiporter. Whether these gills also express a gene coding for an epithelial Na+ channel or Na+/K+/2Cl- cotransporter remains to be demonstrated.

Effects of luminal antigen on intestinal albumin and hyaluronan permeability and ion transport in atopic patients

BACKGROUND: Increased luminal transport of proteins and fluid is part of the inflammatory reaction in inflammatory disease of the bowel and of the airways in allergic diseases and asthma. The objective of this study was to determine intestinal appearance rates of albumin and hyaluronan in vivo in atopic patients allergic to birch, as well as changes in net jejunal transport of monovalent ions and water induced by the antigen. METHODS: Secretion studies were performed with the use of a segmental jejunal perfusion system with a small two-balloon, six-channel tube. The intestinal mucosa was challenged with birch allergen in patients allergic to birch and in matched control subjects (n = 12 in both groups). RESULTS: In patients, but not in control subjects, the luminal antigen induced a net increase in albumin of 2689 ± 567 μg/cm/hr and in hyaluronan of 2609 ± 737 ng/cm/hr (p < 0.01 vs control subjects in both cases). Furthermore, basal net absorption of Cl- ions, Na+ ions, and water was converted to a net secretion after antigen challenge. CONCLUSION: Exposure to antigen normally acting on the respiratory tract induced increased permeability of the gastrointestinal mucosa. This would suggest less organ specificity and more general allergic recognition shared by several immunocompetent tissues in the body, probably mediated by circulating IgE antibodies. (J ALLERGY CLIN IMMUNOL 1996;97:1225-32.)

Calculation of the Reversal Potential of the Na+/Ca++ Exchanger Through the Time Course of the Calcium Paradox: A Model Study

The mode of action of the Na/Ca exchanger was calculated during calcium paradox injury. Several different conditions were assumed and the resulting reversal potential was calculated continuously according to the following equation: E_{Na-Ca} = 3*E_{Na}-2*E_{Ca}. The variables were The intracellular Na+ and Ca++ concentrations, and the membrane potential. In the calculations, various combinations of the variable parameters were selected to simulate the most actual conditions during a Ca-Paradox experiment. The possible role of the Na/Ca exchanger in the ethiopathogenesis of the Ca-Paradox injury, or rather whether the exchanger could be involved in the production of the Ca overload observed in reperfused hearts, is investigated. At rest the driving force indicates a net extrution of calcium ions via the Na/Ca exchanger. The exchanger is said to be in the ÒexitÕ mode. As the cell depolarizes, the membrane potential approaches the reversal potential for the exchanger. When the membrane potential is equal to the reversal potential, the exchanger does not cause any net counter transport of ions. If the cell depolarizes further, the exchanger brings calcium into the cell from the extracellular space. Hence, the exchanger is said to be in the ÒentryÓ mode. In the calculations, the mode of action of the exchanger was calculated in response to the changes in the participating potentials Em, ENa, ECa. However, in most of the assumed conditions, the exchanger was calculated to be in the exit mode, indicating a removal of calcium rather than an overload. This study points out that theoretically the exchanger alone may not explain the Ca-overload observed in the reperfused hearts in Ca-Paradox experiments.

Inhibitory effect of sodium ursodeoxycholate on basal and stimulated short-circuit current across the isolated toad skin

The effect of sodium ursodeoxycholate (U) on short-circuit current (SCC), an index of basal and stimulated net ion transport across isolated skins of Bufo arenarum toads, was tested. U inhibited basal SCC when added to the epidermal side of the skins. The inhibitory effect was reversible after rinsing the preparation during 60 min. U also inhibited the natriferic response to oxytocin, db-cAMP and theophylline by 82%, 49% and 47%, respectively. Inhibition of SCC by exposure to U was reversed by the polyene antibiotic nystatin. In turn, SCC induced by nystatin in the amiloride-treated skin was insensitive to U and blocked by ouabain, a Na +, K +-ATPase inhibitor. These results strongly suggest that the effect of U is exerted at the apical membrane of sodium transporting cells, and rule out the existence of an additional site of inhibitory action of U.

Atrial natriuretic peptide inhibited the natriferic and hydrosmotic effects of arginine vasotocin on toad skin

The effect of rat atrial natriuretic peptide (rANP) on hormonal stimulated osmotic water permeability (Jw, hydrosmotic effect) and net ion transport (short-circuit current, SCC, natriferic effect) was studied on toad skin, a tissue with functional similarities to the mammalian distal nephron, in order to assess actions on transport mechanisms. Rat atrial natriuretic peptide, rANP-99-126 (rANP) inhibited stimulated SCC and Jw to submaximal concentrations of arginine vasotocin (AVT) at a site before cyclic AMP generation. The angiotensin-converting enzyme inhibitor (ACEI) MK-422 did not modify the inhibitory effect of ANP in the stimulated Jw.

Atrial natriuretic peptide inhibited the natriferic and hydrosmotic effects of arginine vasotocin on toad skin

The effect of rat atrial natriuretic peptide (rANP) on hormonal stimulated osmotic water permeability (Jw, hydrosmotic effect) and net ion transport (short-circuit current, SCC, natriferic effect) was studied on toad skin, a tissue with functional similarities to the mammalian distal nephron, in order to assess actions on transport mechanisms. Rat atrial natriuretic peptide, rANP-99-126 (rANP) inhibited stimulated SCC and Jw to submaximal concentrations of arginine vasotocin (AVT) at a site before cyclic AMP generation. The angiotensin-converting enzyme inhibitor (ACEI) MK-422 did not modify the inhibitory effect of ANP in the stimulated Jw.

F-Actin Differentially Alters Epithelial Transport and Barrier Function

Vectorial ion transport and barrier function are two fundamental and defining properties of all epithelial cells. To define the role of F-actin in these dual properties, we studied the effects of two probes of cytoskeletal function on the well-differentiated human intestinal epithelial cell line T84: cytochalasin D, a fungal metabolite widely used to disrupt microfilament function by an uncertain mechanism, and phalloidin, a more specific agent which binds and stabilizes F-actin with high affinity, thus preventing actin depolymerization. T84 cells grown on collagen-coated permeable supports were studied by dual voltage-current clamping; transepithelial resistance to passive ion flow (R, an indirect measure of junctional integrity) and short-circuit current (a measure of net electrogenic ion transport response to the adenylate cyclase activator forskolin was preserved. In contrast, stabilization of F-actin by incubation with phalloidin for up to 24 hr produced no change in R but caused a profound inhibition of cAMP-stimulated short-circuit current. Thus, cytochalasin D was found to perturb barrier but not transport function of T84 monolayers; conversely, stabilization of F-actin by phalloidin was found not to affect barrier function but markedly attenuated electrogenic ion transport. The results suggest that the dual properties of barrier function and ion transport in intestinal epithelia may be differentially influenced by dynamic alterations in F-actin.

Ion transport systems in membrane vesicles isolated from crustacean tissues

AbstractStudies with membrane vesicles isolated from crustacean gill have offered evidence for three major transport systems believed to play central roles in ion transport across the gill epithelium. First, ATP‐dependent sodium/potassium and sodium/ammonium exchanges have been demonstrated in Na+ + K+ ‐ATPase‐rich membrane preparations, supporting the concept that ammonium ion can serve as an effective counterion for sodium transport from cytosol to blood. Second, an amiloride‐sensitive Na+ /H+ antiporter, demonstrated using a pH‐sensitive fluorescent dye, has been shown to be electrogenic, apparently exchanging 2 sodium ions for 1 hydrogen ion. These two transport systems, the first in the basolateral membrane and the second likely in the apical membrane, can achieve net transport of sodium ions from water to blood. Third, a Cl−/HCO3− exchanger has been demonstrated in membrane vesicles from crab gill, most likely playing a central role in the sodium‐independent transfer of chloride across the epithelium. Finally, although no direct studies of calcium transport in crab gill have been reported, indirect evidence from other tissues suggests that part of the calcium flux across the gill may be mediated by Ca2+ /H+ exchange. © 1993 Wiley‐Liss, Inc.

Epithelial ion transport in the ileal J-pouch after proctocolectomy in the rat.

In ulcerative colitis and polyposis coli, creation of an ileal pouch with ileoanal anastomosis after proctocolectomy has become a common surgical method. The aim of our study was to characterize the adaptation of the epithelial ion transport function in the pouch by using electrophysiologic techniques. Proctocolectomy and ileoanal anastomosis was performed in rats either with (pouch) or without (control) creation of an ileal J-pouch. To characterize the epithelial barrier function, impedance analysis was performed 6 months after surgery. Epithelial resistance was 29 +/- 2 omega.cm2 in controls and was unchanged in the pouch (28 +/- 4 omega.cm2; NS). In contrast, subepithelial resistance increased from 33 +/- 3 omega.cm2 to 54 +/- 5 omega.cm2 (P < 0.01) owing to work hypertrophy of the muscle layers in the pouch. To detect changes in net ion transport, ion tracer fluxes were measured in the Ussing chamber. In control ileum, absorptive net Na and Cl fluxes of similar magnitude were present, indicating that electroneutral NaCl absorption was the predominant ion transport system. Neither Isc nor net Na and Cl fluxes were significantly altered in the pouch. Glucose-coupled Na absorption was measured as the 3-o-methyl-glucose-induced increase in Isc. Km remained unaltered, while Vmax decreased from 7.5 +/- 2.1 mu eq.h-1 cm-2 in controls to 1.7 +/- 0.8 mu eq.h-1 cm-2 (P < 0.05) in the pouch. Then, maximal transport capacity for electrogenic Cl secretion was measured as the Cl-induced increase in Isc blockable by serosal bumetanide (in the presence of theophylline and prostaglandin E1).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional differences in the response to platelet-activating factor in rabbit colon.

1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known to stimulate anion secretion in the distal colon. Since there are regional differences in ion transport within the colon, the influence of platelet-activating factors on ion transport and epithelial permeability has been studied in rabbit caecum and distal colon mounted in Ussing chambers. 2. The effect of platelet-activating factor (1-50 nmol/l) on net electrogenic ion transport was to stimulate a biphasic increase in short-circuit current in the distal colon but not in the caecum. The platelet-activating factor-induced rise in short-circuit current was shown by ion replacement and pharmacological inhibitor studies to be consistent with chloride and bicarbonate secretion in the early phase, but with chloride secretion alone in the later phase. The effect on ion transport was specific and reversible and was enhanced by 0.25% BSA. 3. Colonic permeability, assessed by transmucosal resistance and mannitol flux, was increased by platelet-activating factor in both the distal colon and the caecum. This was consistent with an effect on platelet-activating factor on the paracellular pathway, because resistance decreased even when transcellular chloride transport was inhibited by frusemide or ion replacement. A specific platelet-activating factor antagonist (U66985) inhibited the effects of platelet-activating factor in both the distal colon and the caecum. 4. The results show that platelet-activating factor stimulates anion secretion only in the distal colon, but increases permeability in both the caecum and the distal colon.

Vitamin A deficiency and colonic electrogenic absorption and secretion in the rat.

The effects of vitamin A deficiency on electrogenic transport in the colon were examined in rats made vitamin A deficient at weaning by feeding a vitamin A deficient diet for 40 days. A pair fed control group was given the same diet but supplemented with soluble vitamin A in their drinking water. The basal and stimulated electrogenic secretory and absorptive functions of the muscle stripped proximal, mid, and distal colon were examined in vitro using the short circuit current (Isc) as the index of net ion transport. A significant increase in the basal and secretory Isc (mainly Cl-ions) induced by the cholinergic agonist bethanechol was observed in the mid-colon of the vitamin A deficient rats. In the distal colon, however, vitamin A deficiency caused a significant reduction in both the basal and secretory Isc response to bethanechol compared with the vitamin A supplemented pair fed control. Secretory Isc induced by dibutyryl cyclic adenosine monophosphate was not significantly altered by vitamin A deficiency. The condition abolished the response of the distal colon to luminal amiloride (0.1 mmol/l). Thyroid hormone induced reduction in the distal colonic response to aldosterone is implicated in this lack of response. This is the first experimental linkage between vitamin A action, the thyroid hormone and aldosterone on colonic function. The colonic changes induced by vitamin A deficiency, namely hypersecretion and a reduced electrogenic distal absorptive function, together with the previously described small intestine hypersecretion may be the underlying basis for the diarrhoea observed in human and animal vitamin A deficiency.

Effects of lofexidine, an alpha 2-adrenoreceptor agonist, on ocular blood flow and ion transport of rabbit iris-ciliary body.

The effect of topical unilateral application of lofexidine, an alpha 2-agonist, on ocular regional blood flow was tested in anesthetized rabbits using radiolabeled microspheres. A significant reduction in blood flow was found only in the ciliary body of the treated eye at 1 hr after lofexidine treatment. However, the IOP of both eyes was decreased significantly at 30 and 60 min post lofexidine treatment. Yohimbine (i.v.) blocked this IOP lowering effect, but only partially prevented the blood flow response. In addition, no significant difference was found in either basal or amphotericin-B stimulated short-circuit current or potential difference of the isolated rabbit iris-ciliary body after 30 minutes of lofexidine treatment. These observations suggest that the IOP lowering effect of lofexidine appears to be mediated by alpha 2-receptors but unrelated to the reduction in the ocular blood flow and net electrogenic ion transport.