Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “METHAZOLAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1983

The effect of topically administered carbonic anhydrase inhibitors on aqueous humor dynamics in rabbits.

Repeated topical administration of 2.5% trifluormethazolamide, a halogenated derivative of methazolamide, resulted in a unilateral decrease in intraocular pressure in rabbits. Mean (+/- S.E.M.) baseline intraocular pressure (19.8 +/- 2.1 mm Hg) was significantly (P less than .05) decreased 30 minutes (16.1 +/- 2.2 mm Hg) and 60 minutes (15.8 +/- 2.7 mm Hg) after drug administration. Trifluormethazolamide did not alter outflow facility. Aqueous humor flow calculated from the tonographic data was reduced 44% and flow measured by fluorophotometry was reduced 29%. Topical delivery of trifluormethazolamide decreased the level of carbon dioxide in the aqueous humor in the treated eye in a manner similar to that observed after systemic administration of carbonic anhydrase inhibitors. Topical administration of 10% acetazolamide did not decrease intraocular pressure. However, topical administration of either trifluormethazolamide or acetazolamide before oral administration of water resulted in a blunting of the water-induced ocular hypertensive response.

Acetazolamide↗
PubMed1988

Enhancement of the ocular hypotensive effect of acetazolamide by diflunisal.

We studied the effect of diflunisal on intraocular pressure in patients with glaucoma who were receiving maximally tolerated therapy. Diflunisal therapy, 500 mg twice daily, was started in 48 patients for one week. No changes were made in their regular antiglaucoma medications. Intraocular pressure was reduced an additional 3.8 +/- 3.1 mm Hg (+/- S.D.) in the acetazolamide-treated patients (P less than .0001) and 1.6 +/- 1.5 mm Hg in methazolamide-treated patients (P less than .02), while no significant reduction in intraocular pressure was found in patients receiving topical medications alone. In 15 acetazolamide-treated patients, total plasma concentrations of acetazolamide after diflunisal therapy were significantly higher than the prediflunisal levels, suggesting a modest decrease in renal excretion. In seven acetazolamide-treated patients, free plasma concentrations of acetazolamide were found to increase 5.6-fold after diflunisal therapy. We concluded that diflunisal potentiated the ocular hypotensive effect of acetazolamide by increasing its free plasma level.

Acetazolamide↗
PubMed1989

Intraocular pressure effects of carbonic anhydrase inhibitors in primary open-angle glaucoma.

We tested the effect on intraocular pressure of three commonly used oral carbonic anhydrase inhibitor preparations in a controlled, randomized, comparative study on patients with primary open-angle glaucoma. Preparations tested included acetazolamide tablets, acetazolamide Sequels, and methazolamide tablets. The effect of the three carbonic anhydrase inhibitors was assessed by using a statistical modeling approach as well as by evaluating the average maximum reduction in intraocular pressure for each preparation. Dosage and time effects were also determined. As expected, each drug preparation was more effective in reducing intraocular pressure when administered to a patient who had already been treated with the carbonic anhydrase inhibitor preparation. The amount of intraocular pressure lowering was directly related to dose for both acetazolamide preparations. Of particular interest was the finding that maximal rapid reduction of intraocular pressure was obtained with a 500-mg dosage of acetazolamide tablets.

Acetazolamide↗
PubMed1991

Localization and activity of renal carbonic anhydrase (CA) in CA-II deficient mice.

A null allele at the mouse Car 2 locus was induced by ethylnitrosurea; mice homozygous for the new allele lack the carbonic anhydrase (CA)-II isoenzyme. The expression of this genetic lesion was investigated by: (1) using tissue fractionation techniques to determine localization and activity of CA in the kidney, and (2) examining renal response to CA inhibition in CA-II deficient mice (CAD), in normal (N) mice and in heterozygous litter mates (LM). N and LM mice had CA activity in proximal tubule brush border membranes and cytosol. CA activity was also localized to membranes and cytosol of the outer medullary region. CAD mice lacked cytosolic activity but had normal CA activity in all membranes examined. All membrane associated CA had 2-8-fold lower sulfonamide sensitivity than cytosolic CA. These inhibition characteristics suggest that the membrane enzyme is CA-IV. Baseline urinary excretion of Na+, K+, and HCO3- was similar in all groups. Urine pH and Cl- excretion were higher and titratable acid output was lower in CAD mice. Inhibition of CA (methazolamide, 25 mg/kg) led in all groups to equivalent increments of urine pH, urine flow, and HCO3-, Na+, and K+ excretion. Cl- excretion was unchanged. Thus the extent of the genetic deficiency of CA-II mice extends to the kidney cytosol but does not alter membrane localization or levels of CA, probably CA-IV. The similar response to CA inhibition in CAD mice suggests that CA-IV, the membrane bound isoenzyme is the important isoenzyme in proximal tubule HCO3- reabsorption.

Animals↗
PubMed1991

NaCl absorption in the rabbit ileum. Effect of acid-base variables.

In vivo and in vitro studies suggest that acid-base variables regulate ion transport in the rabbit ileum. The relative importance of these variables on active Na+ and Cl- absorption has not been defined. Isolated, stripped ileal segments were studied under short-circuited conditions in the Ussing flux chamber. Unidirectional 22Na and 36Cl fluxes were measured after changes in bathing solution pH, PCO2, and/or [HCO3-]. When pH was decreased from 7.6 to 7.1, net flux of Na+ increased from 0.1 +/- 0.7 to 2.6 +/- 0.7 mu Eq/cm2 per hour and net flux of Cl- increased from -2.0 +/- 0.9 to 1.3 +/- 0.6 mu Eq/cm2 per hour. These changes were rapid in onset, completely reversible, and accounted for by changes in mucosal-to-serosal fluxes of these ions. They were accompanied by small decreases in short-circuit current, but there were no changes in residual flux. These pH effects were not inhibited by the presence of luminal bumetanide (1 mmol/L), furosemide (1 mmol/L), hydroflumethiazide (1 mmol/L), or 4,4'-diisothiocyanostilbene-2,2'-disulfonate (1 mmol/L), or by the carbonic anhydrase inhibitor methazolamide (1 mmol/L). When data from all combinations of acid-base conditions were combined and analyzed by linear regression, pH was the only variable that correlated with mucosal-to-serosal fluxes (r = -0.84) and net flux (r = -0.85) for Na+, mucosal-to-serosal fluxes (r = -0.96) and net flux (r = -0.99) for Cl-, and short-circuit current (r = 0.97). These findings suggest that extracellular pH modulates active Na+ and Cl- absorption in the rabbit ileum.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Inhibition properties and inhibition kinetics of an extracellular carbonic anhydrase in perfused skeletal muscle.

We have investigated the properties of the carbonic anhydrase which is functionally available to CO2 and HCO3- in the capillary bed of skeletal muscle. We used essentially the indicator-dilution technique of Effros and Weissman (J. Appl. Physiol. 47, 1090-1098, 1979). Into hindlimbs of rabbits perfused with dextran solution we injected boli containing H14CO3- or 36Cl-, and 3H-dextran (MW 80 000) as an intravasal indicator, and observed the washout of these indicators by fractionated collection and analysis of the venous effluent. In agreement with previous studies we found that addition of 10(-4) M of the carbonic anhydrase inhibitor acetazolamide to the perfusate considerably speeds up the washout of 14C, reducing the extraction of 14C from 0.72 to 0.45. A half-maximal effect on 14C extraction was achieved with 1 x 10(-6) M acetazolamide (IC50). The carbonic anhydrase inhibitors methazolamide and benzolamide both yielded IC50 values of 10(-5) M. This pattern of inhibitory potency of the three sulfonamides is incompatible with their inhibitory effects on the two known cytosolic isoenzymes of skeletal muscle, CAII and CAIII. While cells take up acetazolamide and benzolamide extremely slowly, with half-times of several minutes to hours, the effect of both sulfonamides on 14C washout occurred very rapidly: less than 1 min, probably not more than a few seconds, were necessary to achieve inhibitory effects. We conclude that (1) a tissue carbonic anhydrase converts the injected H14CO3- quickly into 14CO2 which then diffuses into the intracellular space thus causing a washout of 14C that is much slower than that of the intravasal indicator or that of 36Cl-, (2) this carbonic anhydrase is not intra- but extracellular and presumably membrane-bound, and (3) its properties suggest that it is distinct from the well-known cytosolic carbonic anhydrases and represents a different isoenzyme.

Acetazolamide↗
PubMedDate not supplied

Laryngeal CO2 receptors: influence of systemic PCO2 and carbonic anhydrase inhibition.

Responses of laryngeal receptors selected for their responsiveness to 10% intralaryngeal CO2 were recorded in single fibers of the superior laryngeal nerve at a wide range of systemic PCO2 values and before and after carbonic anhydrase inhibition in anesthetized, paralyzed, ventilated cats. Carbonic anhydrase was inhibited, locally, by perfusing the upper airways with either acetazolamide or methazolamide (10(-2) M) or systemically, by injecting acetazolamide intravenously (5, 10, or 25 mg/kg). Of the 58 receptors studied, 55 decreased their discharge rate in response to 10% intralaryngeal CO2, whereas 3 increased their discharge in response to intralaryngeal CO2. The majority of these receptors also increased their discharge rate in response to positive laryngeal pressure. Neither increased nor decreased systemic PCO2 influenced the receptors' baseline discharge rate or their response to intralaryngeal CO2. Topical inhibition of carbonic anhydrase did not consistently alter the maximal inhibitory response to CO2 or the initial rate of change of receptor activity. On the other hand, intravenous injections of acetazolamide caused, within 30 sec, a consistent attenuation of both the initial rate of change and the maximal inhibitory response to intralaryngeal CO2. These results indicate that the sub-set of laryngeal receptors that are sensitive to intralaryngeal CO2 are not responsive to changes in systemic PCO2. The carbonic anhydrase inhibition experiments show that this enzyme plays an important role in the ability of these receptors to detect both transient and steady-state changes in intralaryngeal CO2.

Acetazolamide↗
PubMed1989

Light-evoked changes in extracellular pH in frog retina.

Light-induced changes in extracellular H+ concentration (delta pH0) were studied with intraretinal H(+)-sensitive double-barreled microelectrodes in frog eyecup and isolated retina preparations. The most prominent delta pH0 were found in the inner plexiform layer, as pH increases (alkalinizations) at light onset and offset. With a small-spot stimulus (0.3 mm dia.), 30 sec in duration, the delta pH0 were relatively small (0.03 pH units), and long lasting (peak at 25-30 sec). They were enhanced by flicker (0.3 Hz). Depth profiles paralleled those of the field potentials (PNR/M-wave), the ON delta pH0 peaking 40 microns more proximal than the OFF response. The delta pH0 exhibited surround antagonism, which was blocked by tetrodotoxin (TTX), indicating an independence from action potentials. The mechanism for these pH increases in proximal retina is not yet understood. In the subretinal space diffuse retinal illumination produced a small pH increase, consistent with a presumed decrease in photoreceptor lactate production. Inhibition of carbonic anhydrase (CA) with acetazolamide or methazolamide increased both the proximal and distal retinal delta pH0, suggesting that CA is involved in buffering retinal pH.

Acetazolamide↗
PubMed1993

Mechanism of bicarbonate secretion in rat (Rattus rattus) colon.

1. Colonic HCO3 secretion was measured as the residual flux in male Sprague-Dawley rats (Rattus rattus). 2. Basal HCO3 secretion was increased by 1 mM dibutyryl cyclic AMP (dbcAMP) and was reduced to baseline by 0.1 mM methazolamide (Mtz) but not by SITS (1 mM), DIDS (1 mM) or amiloride (1 mM). 3. In vivo, intravenous vasoactive intestinal peptide increased HCO3 secretion and prior perfusion with 1 mM Mtz prevented this increase. 4. These results suggest that the source of basal and cAMP-stimulated HCO3 secretion is, in part, intracellular and requires the action of carbonic anhydrase.

Animals↗
PubMed1991

Carbonic anhydrase inhibitors are antiarthritic in the rat.

Adjuvant-induced arthritis in rats was attenuated by the therapeutic administration of carbonic anhydrase inhibitors. Female Lewis rats with established disease were treated daily (day 18 through day 50) with various carbonic anhydrase inhibitors; oedema and joint integrity (X-ray) were determined post-treatment. Acetazolamide, ethoxzolamide, methazolamide, and dichlorphenamide reduced paw oedema and attenuated the deterioration of the joints of rats with adjuvant arthritis. However, no carbonic anhydrase inhibitor tested possessed significant, acute, anti-inflammatory activity in the carrageenan-paw oedema test. The activity of carbonic anhydrase inhibitors in the chronic model of inflammation may be due to their reported inhibition of bone resorption.

Acetazolamide↗
PubMed2004

Alkalization of larval mosquito midgut and the role of carbonic anhydrase in different species of mosquitoes.

We have previously demonstrated the involvement of carbonic anhydrase (CA) in the alkalization mechanism of the Aedes aegypti larval midgut. In this study, we used Hansson's histochemistry to examine the distribution of the enzyme in the midgut of six different species of mosquito larvae (Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, Culex nigripalpus, Ochlerotatus taeniorhynchus, Anopheles quadrimaculatus). Additionally, we quantitated CA content in the gastric caeca, anterior and posterior midgut of fourth instar larvae from these species using the 18O isotope exchange method coupled to mass spectrometry. We also tested the effect of CA inhibitors such as methazolamide and acetazolamide in the alkalization of the midgut for these species. Our results indicate that CA is present in the larval midgut of the species studied and that it appears to be associated with the posterior midgut and gastric caeca in some species and with the anterior midgut in others. CA inhibitors appear to have a profound effect on the alkalization mechanism of the midgut with lethal consequences for most of the species tested.

Acetazolamide↗
PubMed1992

Acetazolamide-like carbonic anhydrase inhibitors with topical ocular hypotensive activity.

New carbonic anhydrase (EC 4.2.1.1) inhibitors were synthesized as potential drugs for the topical treatment of glaucoma. They were obtained by substituting the acetyl group of acetazolamide and methazolamide with bicarboxylic acids of different chain length (C4-C6). The terminal carboxyl was either kept free or esterified with alcohols of different size (C1-C12). A gamma-aminovaleric derivative was also prepared. All compounds proved active as carbonic anhydrase inhibitors in vitro, with an average IC50 of about 0.5 microM. Some proved also to be topically active in vivo in lowering the artificially elevated intraocular pressure in rabbits. The most active compound, carrying a succinic acid side chain, is the most soluble in aqueous buffers. Its duration of action is about 8 h and it is under evaluation as a topical antiglaucoma drug. It is hypothesized that the duration of action could be longer in compounds having both the same high water solubility and partition coefficient.

Acetazolamide↗
PubMed2005

Functional interaction of carbonic anhydrase and chloride/bicarbonate exchange in human platelets.

Recently, our laboratory has reported the presence of one acidifying Cl-/HC exchange mechanism in human platelets. This paper demonstrates that this exchanger decreases its activity after inhibition of carbonic anhydrase. BCECF-loaded platelets, previously equilibrated in a bicarbonate/CO2 buffered solution, were resuspended in a Hepes-buffered, chloride-free (glucuronate) medium to produce a pHi increase. After addition of 50 mM NaCl, pHi fell rapidly reaching steady state in the succeeding 400 s. The recovery in chloride-containing solution was in contrast to the effect of a similar change in osmolarity by addition of 50 mM sodium glucuronate that produced a significantly slower variation of pHi. Alkali loads produced by 25 mM TMA were also counteracted by HC equivalent efflux via Cl-/HC exchange. The present study shows that the efflux of HC was slower when the platelets were previously incubated in 100 microM methazolamide. As a conclusion, the recovery of pHi from alkalosis by Na-independent Cl-/HC exchange is facilitated in platelets by the enzymatic activity of the carbonic anhydrase.

Bicarbonates↗
PubMed2004

Gramicidin-perforated patch recording revealed the oscillatory nature of secretory Cl- movements in salivary acinar cells.

Elevations of cytoplasmic free calcium concentrations ([Ca(2+)](i)) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl(-) through Ca(2+)-activated Cl(-) channels, while Cl(-) enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na(+)-K(+)-2Cl(-) cotransporter (NKCC) and/or parallel operations of Cl(-)-HCO(3)(-) and Na(+)-H(+) exchangers, located in the basolateral membrane. To characterize the contributions of those activities to net Cl(-) secretion, we analyzed carbachol (CCh)-activated Cl(-) currents in submandibular acinar cells using the "gramicidin-perforated patch recording configuration." Since the linear polypeptide antibiotic gramicidin creates monovalent cation-selective pores, CCh-activated Cl(-) currents in the gramicidin-perforated patch recording were carried by Cl(-) efflux via Cl(-) channels, dependent upon Cl(-) entry through Cl(-) transporters expressed in the acinar cells. CCh-evoked oscillatory Cl(-) currents were associated with oscillations of membrane potential. Bumetanide, a loop diuretic, decreased the CCh-activated Cl(-) currents and hyperpolarized the membrane potential. In contrast, neither methazolamide, a carbonic anhydrase inhibitor, nor elimination of external HCO(3)(-) had significant effects, suggesting that the cotransporter rather than parallel operations of Cl(-)-HCO(3)(-) and Na(+)-H(+) exchangers is the primary Cl(-) uptake pathway. Pharmacological manipulation of the activities of the Ca(2+)-activated Cl(-) channel and the NKCC revealed that the NKCC plays a substantial role in determining the amplitude of oscillatory Cl(-) currents, while adjusting to the rate imposed by the Ca(2+)-activated Cl(-) channel, in the gramicidin-perforated patch configuration. By concerting with and being controlled by the cation steps, the oscillatory form of secretory Cl(-) movements may effectively provide a driving force for fluid secretion in intact acinar cells.

Angiogenesis Inhibitors↗
PubMed1997

Penetration into the anterior chamber via the conjunctival/scleral pathway.

The importance of the conjunctival/scleral pathway as a route of entry into the ciliary body, and in particular uptake and deposition by vessels, was investigated. A constant concentration of methazolamide analogs as well as 6-carboxyfluorescein (6-CB) and rhodamine B (RB) was maintained on either the cornea or the conjunctiva/sclera tissue, the latter excluding the cornea. The solutions were applied with the use of a cylindrical well affixed to the cornea of an anesthetized white rabbit. After two hours, concentrations of drug or dye were measured in cornea, aqueous humor or iris/ciliary body for both routes of entry. Confocal microscopy methods were used to determine reflected fluorescence images for 6-CB and RB. Carbonic anhydrase inhibition, partitioning, solubility and intraocular pressure (IOP) measurements were also determined. Permeability calculations were estimated for drug diffusing against aqueous flow within the posterior chamber. The conjunctival/scleral route of entry produced higher iris/ciliary body concentrations for all compounds except for the lipophilic RB. Confocal microscopy results suggested that drug is gaining entry into the ciliary body through vessel uptake in the sclera. Following entry of drug into the conjunctival/scleral tissue, a significant portion enters scleral vessels and deposits within the ciliary body. Calculations are given that indicate that once drug penetrates the cornea it is highly unlikely drug diffuses through the pupil against aqueous flow to enter the posterior chamber and reach the ciliary body.

Administration, Topical↗
PubMed1992

Barium- or quinine-induced depolarization activates K+, Na+ and cationic conductances in frog proximal tubular cells.

1. Frog proximal tubular cells were fused into giant cells. We measured membrane potential (Vm), its changes (delta Vm), and current-induced voltage changes (delta psi) in single cells, during control and experimental states. Each cell served as its own control. 2. In the presence of a physiological Ringer solution, the transference number for potassium (tK) was 0.50. Barium (3 mM) reduced membrane conductance (Gm) by 50%; low-Cl- solutions and low-Na+ solutions also diminished Gm, by 52 and 30%, respectively. The association of barium and low-NaCl solutions decreased Gm to approximately 38% of control, indicating that the impermeant substitute of a physiological ion may interact with other pathways; alternatively, blockade of steady-state conductances may activate physiologically silent processes. 3. In an attempt to enhance the contribution of the partial K+ conductance (GK) to Gm, fused cells were exposed to low-Cl- solutions, containing in addition 0.1 mM-methazolamide, to inhibit the rheogenic Na(+)-HCO3-symport, and 1 microM-amiloride, to block Na+ conductance (GNa). tK went up to 0.83. 4. The high tK preparation was challenged with barium (3 mM) or quinine (Quin, 1 mM). These blockers produced large depolarizations (approximately 60 mV), however, although Gm decreased along early- and mid-depolarization, Gm plateaued and eventually it increased with larger and larger depolarization. 5. Depolarization-associated increase in Gm reflects activation of other conductances. These are Na+, cationic, and K+ conductance(s) poorly sensitive to quinine or barium. In the presence of Ba(2+)- or Quin-induced depolarization, injection of depolarizing current produces delayed increase in conductance. 6. Depolarization-induced activation of cationic conductance (Gcat) and GNa results in enlargement of the K+ electrochemical potential difference, to about 70 mV; this difference allows recycling of K+ ions outwards, since a GK is still detected and may contribute up to 38% of the total conductance.

Amiloride↗
PubMed2006

Epithelial carbonic anhydrases facilitate PCO2 and pH regulation in rat duodenal mucosa.

The duodenum is the site of mixing of massive amounts of gastric H+ with secreted HCO3-, generating CO2 and H2O accompanied by the neutralization of H+. We examined the role of membrane-bound and soluble carbonic anhydrases (CA) by which H+ is neutralized, CO2 is absorbed, and HCO3- is secreted. Rat duodena were perfused with solutions of different pH and PCO2 with or without a cell-permeant CA inhibitor methazolamide (MTZ) or impermeant CA inhibitors. Flow-through pH and PCO2 electrodes simultaneously measured perfusate and effluent pH and PCO2. High CO2 (34.7 kPa) perfusion increased net CO2 loss from the perfusate compared with controls (pH 6.4 saline, PCO2 approximately 0) accompanied by portal venous (PV) acidification and PCO2 increase. Impermeant CA inhibitors abolished net perfusate CO2 loss and increased net HCO3- gain, whereas all CA inhibitors inhibited PV acidification and PCO2 increase. The changes in luminal and PV pH and [CO2] were also inhibited by the Na+-H+ exchanger-1 (NHE1) inhibitor dimethylamiloride, but not by the NHE3 inhibitor S3226. Luminal acid decreased total CO2 output and increased H+ loss with PV acidification and PCO2 increase, all inhibited by all CA inhibitors. During perfusion of a 30% CO2 buffer, loss of CO2 from the lumen was CA dependent as was transepithelial transport of perfused 13CO2. H+ and CO2 loss from the perfusate were accompanied by increases of PV H+ and tracer CO2, but unchanged PV total CO2, consistent with CA-dependent transmucosal H+ and CO2 movement. Inhibition of membrane-bound CAs augments the apparent rate of net basal HCO3- secretion. Luminal H+ traverses the apical membrane as CO2, is converted back to cytosolic H+, which is extruded via NHE1. Membrane-bound and cytosolic CAs cooperatively facilitate secretion of HCO3- into the lumen and CO2 diffusion into duodenal mucosa, serving as important acid-base regulators.

Acid-Base Equilibrium↗
PubMed2003

Acid-base effects on intestinal Cl- absorption and vesicular trafficking.

In rat ileum and colon, apical membrane Cl(-)/HCO(3)(-) exchange and net Cl(-) absorption are stimulated by increases in Pco(2) or [HCO(3)(-)]. Because changes in Pco(2) stimulate colonic Na(+) absorption, in part, by modulating vesicular trafficking of the Na(+)/H(+) exchanger type 3 isoform to and from the apical membrane, we examined whether changes in Pco(2) affect net Cl(-) absorption by modulating vesicular trafficking of the Cl(-)/HCO(3)(-) exchanger anion exchanger (AE)1. Cl(-) transport across rat distal ileum and colon was measured in the Ussing chamber, and apical membrane protein biotinylation of these segments and Western blots of recovered proteins were performed. In colonic epithelial apical membranes, AE1 protein content was greater at Pco(2) 70 mmHg than at Pco(2) 21 mmHg but was not affected by pH changes in the absence of CO(2). AE1 was internalized when Pco(2) was reduced and exocytosed when Pco(2) was increased, and both mucosal wortmannin and methazolamide inhibited exocytosis. Wortmannin also inhibited the increase in colonic Cl(-) absorption caused by an increase in Pco(2). Increases in Pco(2) stimulated ileal Cl(-) absorption, but wortmannin was without effect. Ileal epithelial apical membrane AE1 content was not affected by Pco(2). We conclude that CO(2) modulation of colonic, but not ileal, Cl(-) absorption involves effects on vesicular trafficking of AE1.

Absorption↗