Net fluxes of electrolytes in the rat intestine infected with Moniliformis dubius (Acanthocephala).

The effect of Moniliformis dubius on fluxes of Na+, K+, Cl-, and HCO3-in the rat intestine was determined using a conventional in vivo single-pass perfusion technique. Results for ion and water movements in the uninfected gut were in agreement with previous studies. In the parasitized intestine the jejunal pH was significantly lower than that in control animals, matching the restriction of the parasites to this region of the small intestine. While parasitism did not affect Na+ transport in the distal ileum, Na+ absorption was reduced (pH 7.0), or secretion enhanced (pH 6.0), in the two proximal regions. Cl-absorption was reduced in the distal ileum, but secretion was enhanced in the other two segments. Parasitism also enhanced K+ secretion in all segments. Net H2O absorption was reduced at pH 7.0; at pH 7.0; at pH 6.0 net secretion was also reduced. These changes clearly indicate that a parasite restricted to the jejunum may significantly affect the absorptive and secretory activity of the intestine distal to the site of infection. The results are discussed in the light of current concepts of electrolyte transport. The effect of the parasites on mucosal function distal to their site of attachment is discussed in terms of the release by the parasite of toxin-like substances, changes in the physical-chemical characteristics of the intestinal lumen, and interference with neurohormonal control of gastrointestinal function.     

Influence of nitrate and nitrite on electrolyte transport by the rat small and large intestine

1. The influence of nitrate and nitrite on net absorption of electrolytes (Na+, K+, Cl-) and water from ligated loops was studied at various intestinal sites in rats. 2. Nitrate strikingly reduced Cl- absorption in rat proximal and distal colon, whereas Na+ absorption was reduced only moderately. Nitrite also reduced Cl- absorption in the colon. 3. Nitrate showed no significant effect on electrolyte absorption in the small intestine. 4. The results suggest that Cl-/HCO3- on exchange is the major route of Cl- absorption in the colon, whereas this mechanism seems not to be of importance for Cl- absorption by the small intestine.     

Comparison of VIP-induced electrolyte secretion at three levels in rat small intestine.

Duodenal, jejunal and ileal loops were prepared and an iso-osmotic test solution injected, containing 80 mM Na+, 5-mM K+, 1.2 mM Ca2+, 77 mM Cl-, 10 mM HCO3- and 136 mM mannitol. 14CPEG 4000 was used as a non-absorbable marker and 36Cl was added to measure the bidirectional fluxes. During the 60-min in vivo incubation time, the duodenum actively secreted bicarbonate, a virtually zero flux in the jejunum was observed, whereas the ileum absorbed water and chloride and secreted bicarbonate. The response to the perfused doses of 0.15 to 2.4 nmol.100 g-1.h-1 of VIP (vasoactive intestinal peptide) differed qualitatively and quantitatively in the 3 segments: VIP increased bicarbonate secretion and induced chloride secretion in the duodenum, induced chloride secretion in the jejunum without changing bicarbonate minimal influx, induced bicarbonate secretion and suppressed chloride absorption in the ileum. The minimal dose required was lower in the duodenum (0.3 nmol.100 g-1.h-1) than in the jejunum and ileum (1.2 nmol.100 g-1.h-1). The functional heterogeneity of the small intestine was clearly demonstrated after VIP stimulation.     

Effects of calcium and sugars on intestinal manganese absorption

An in vivo luminal perfusion technique was used to investigate the influence of Ca, Mg, lactose, and glucose on Mn absorption in different segments of the rat intestine. Mn absorption was determined by measuring disappearance of⁵⁴Mn activity from the perfusion solution containing 0.1 or 0.01 mmol/L Mn. Na and water absorption were also determined. Mn absorption decreased during the first 30 min of perfusion to reach a steady state thereafter. Ca (1 mmol/L) inhibited Mn absorption in the proximal jejunum and in the colon, whereas Mn absorption was increased by Ca in the distal jejunum. Mg (1 mmol/L), lactose, and glucose (25 mmol/L each) had no effect on Mn absorption in the jejunum. These results can be explained by a direct interaction of Mn and Ca during transcellular Ca transport in the proximal jejunum and colon. The reason for the stimulatory effect of Ca in the distal jejunum is unknown.     

Effect of size of Trichinella spiralis (Nematode) infections on glucose and ion transport in the rat intestine

An in vivo perfusion technique, using 3 intestinal loops representing the anterior, mid and posterior regions of the rat small intestine, was used to determine intestinal glucose uptake 5 days after infection with Trichinella spiralis. At high levels of infection (3,000 and 6,000 larvae/rat) net glucose absorption by the intestinal mucosa was significantly impaired in all regions of the small intestine when compared to uninfected controls. At low levels of infection (50 larvae/rat) glucose uptake by the mucosa was significantly enhanced in all 3 regions of the small intestine. Intermediate levels of infections (200-1,000 larvae/rat) also enhanced glucose uptake, but only in the anterior regions of the small intestine. When washings from the small intestine of rats infected with 50 larvae/rat were added to the perfusion fluid used on uninfected rats, glucose uptake was also significantly enhanced. These results suggest that at low levels of infection the intestinal lumen contains a metabolite which may affect the mucosal transport of glucose and the related fluxes of H2O, Na+, Cl-, and K+, in the rat intestine. Luminal [H+] and pCO2 decreased from the proximal to distal regions of the small intestine following perfusion; pO2 was significantly decreased in the proximal and distal regions.     

Effect of E. coli heat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice

We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3- Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+ absorption, lower net Cl- absorption, and a negative residual ion flux (J(R)), indicating net HCO3- absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl- (J(s-->m)(Cl)) and decreased net Cl- flux (J(net)(Cl)) accompanied by increases in short-circuit current (I(sc)), potential difference (PD), and tissue conductance (G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon J(s-->m)(Cl) and J(net)(Cl), I(sc), PD, G, and J(R) similar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa.     

Transport of chlorine in the proximal tubule. Its effects on water-electrolyte absorption

Several studies in rat kidney have established that an appreciable fraction of proximal absorption is passive in nature and occurs across the highly conductive paracellular pathway. Passive absorption is generally ascribed to the transepithelial Cl- distribution, luminal Cl- activity (alpha lCl) being higher than plasma Cl- activity (alpha pCl). The inequality alpha lCl greater than alpha pCl generates a transepithelial diffusion potential, lumen positive, which taken together with the chemical potential differences of Cl- and Na+ across the epithelium gives rise to transepithelial electrochemical potential differences for Cl- and Na+ favoring their absorption. The alpha lCl greater than alpha pCl distribution is traditionally ascribed to preferential bicarbonate absorption. We argue that HCO3- absorption alone cannot generate a non equilibrium transepithelial Cl- distribution. Other mechanisms are necessary. Our measurements in amphibian proximal tubule demonstrate that the intracellular Cl- activity, alpha cCl, is higher than the theoretical value predicted for equilibrium. This distribution is the result of two basolateral coupled transport processes (Cl-/HCO3- exchange and Cl-/Na+ cotransport). It contributes to the exit of Cl- from cell to lumen (by passive diffusion and K+/Cl- cotransport), yielding alpha lCl values higher than the theoretical value for equilibrium with regard to plasma. Thus, a small transcellular flux of Cl- (without solvent) proceeds from interstitium to lumen. It compensates the dissipative tendency of a much higher paracellular Cl- absorptive flux (in association with water) on the transepithelial Cl- gradient. The result is a steady-state luminal Cl- distribution above equilibrium, along the major part of the proximal tubule.     

Soybean impairs Na(+)-dependent glucose absorption and Cl- secretion in porcine small intestine

Recent evidence indicates that soybean, which is widely used in animal nutrition, could directly alter intestinal ion and nutrient transport. However, the mechanisms involved are still unknown. The aim of the study was to investigate the effect of three differently treated soybean products on the glucose and Cl- transport capacity in porcine small intestine by the Ussing chamber technique. Jejunal and ileal piglet epithelial tissues were pre-incubated with extracts of raw soybean flour (RSF), heated soybean flour (HSF), or ethanol heat-treated soybean protein concentrate (SPC). The Na(+)-dependent glucose co-absorption capacity was then measured as an increase in the short-circuit current (ISC) after luminal addition of D-glucose. The effect of the soybean products on cAMP-dependent Cl- secretion was measured as the increase in ISC after the addition of the phosphodiesterase inhibitor, theophylline, while nervous regulation of Cl- secretion was investigated by the addition of the enteric neurotransmitters; 5-hydroxytryptamine (5-HT), substance P and vasoactive intestinal polypeptide (VIP). Incubation with RSF and HSF induced a 30% decrease of the Na(+)-dependent glucose absorption capacity in the jejunum. The effect was similar for RSF in the ileum. Theophylline-induced secretion was decreased by 30% after incubation with RSF, HSF and SPC but only in the jejunum. 5-HT-, substance P- and VIP-induced secretion were not altered by incubation with soybean extracts except in the HSF-incubated where the substance P-induced secretion was significantly reduced. In conclusion, soybean contains ethanol-sensitive heat-insensitive compounds impairing Na(+)-dependent glucose absorption in the jejunum and ileum, and ethanol- and heat-insensitive compounds causing an acute impairment of cAMP-dependent jejunal secretion.     

Na+, Li+ and Cl− transport by brush border membranes from rabbit jejunum

Na+, Li+, K+, Rb+, Br-, Cl- and SO4(2-) transport were studied in brush border membrane vesicles isolated from rabbit jejunum. Li+ uptakes were measured by flameless atomic absorption spectroscopy, and all others were measured using isotopic flux and liquid scintillation counting. All uptakes were performed with a rapid filtration procedure. A method is presented for separating various components of ion uptake: 1) passive diffusion, 2) mediated transport and 3) binding. It was concluded that a Na+/H+ exchange mechanism exists in the jejunal brush border. The exchanger was inhibited with 300 microM amiloride or harmaline. The kinetic parameters for sodium transport by this mechanism depend on the pH of the intravesicular solution. The application of a pH gradient (pHin = 5.5, pHout = 7.5) causes an increase in Jmax (50 to 125 pmol/mg protein . sec) with no change in Kt (congruent to 4.5 nM). Competition experiments show that other monovalent cations, e.g. Li+ and NH4+, share the Na+/H+ exchanger. This was confirmed with direct measurements of Li+ uptakes. Saturable uptake mechanisms were also observed for K+, Rb+ and SO4(2-), but not for Br-. The Jmax for K+ and Rb+ are similar to the Jmax for Na+, suggesting that they may share a transporter. The SO4(2-) system appears to be a Na+/SO4(2-) cotransport system. There does not appear to be either a Cl-/OH- transport mechanism of the type observed in ileum or a specific Na+/Cl- symporter.     

CO2-stimulated NaCl absorption in the mouse renal cortical thick ascending limb of Henle. Evidence for synchronous Na +/H+ and Cl-/HCO3- exchange in apical plasma membranes

These experiments evaluated salt transport processes in isolated cortical thick limbs of Henle (cTALH) obtained from mouse kidney. When the external solutions consisted of Krebs-Ringer bicarbonate (KRB), pH 7.4, and a 95% O2-5% CO2 gas phase, the spontaneous transepithelial voltage (Ve, mV, lumen-to-bath) was approximately mV; the net rate of Cl- absorption (JnetCl) was approximately 3,600 pmols s-1 cm-2; the net rate of osmotic solute absorption Jnetosm was twice JnetCl; and the net rate of total CO2 transport (JnetCO2) was indistinguishable from zero. Thus, net Cl- absorption was accompanied by the net absorption of a monovalent cation, presumably Na+, and net HCO3- absorption was negligible. This salt transport process was stimulated by (CO2 + HCO3- ): omission of CO2 from the gas phase and HCO3- from external solutions reduced JnetCl, Jnetosm, and Ve by 50%. Furthermore, 10(-4) M luminal furosemide abolished JnetCl and Ve entirely. The lipophilic carbonic anhydrase inhibitor ethoxzolamide (10(-4) M, either luminal or peritubular) inhibited (CO2 + HCO3-)-stimulated JnetCl, Jnetosm, and Ve by approximately 50%; however, when the combination (CO2 + HCO3-) was absent, ethoxzolamide had no detectable effect on salt transport. Ve was reduced or abolished entirely by omission of either Na+ or Cl- from external solutions, by peritubular K+ removal, by 10(-3) M peritubular ouabain, and by 10(-4) M luminal SITS. However, Ve was unaffected by 10(-3) M peritubular SITS, or by the hydrophilic carbonic anhydrase inhibitor acetazolamide (2.2 x 10(-4) M, lumen plus bath). We interpret these data to indicate that (CO2 + HCO3-)-stimulated NaCl absorption in the cTALH involved two synchronous apical membrane antiport processes: one exchanging luminal Na+ for cellular H+; and the other exchanging luminal Cl- for cellular HCO3- or OH-, operating in parallel with a (CO2+ HCO3-)-independent apical membrane NaCl cotransport mechanism.     

Ion exchangers mediating NaCl transport in the renal proximal tubule

We have studied the mechanisms of NaCl transport in the mammalian proximal tubule. Studies of isolated brush-border membrane vesicles confirmed the presence of Na+-H+ exchange and identified Cl(-)-formate and Cl(-)-oxalate exchangers as possible mechanisms of uphill Cl- entry. We found that formate and oxalate each stimulate NaCl absorption in microperfused proximal tubules. Stimulation of NaCl absorption by formate was blocked by the Na+-H+-exchange inhibitor EIPA, whereas stimulation by oxalate was blocked by omission of sulfate from the perfusion solutions. These observations were consistent with recycling of formate from lumen to cell by H+-coupled formate transport in parallel with Na+-H+ exchange and recycling of oxalate by oxalate-sulfate exchange in parallel with Na+-sulfate cotransport. Using isoform-specific antibodies, we found that NHE1 is present on the basolateral membrane of all nephron segments, whereas NHE3 is present on the apical membrane of cells in the proximal tubule and the loop of Henle. The inhibitor sensitivity of Na+-H+ exchange in renal brush-border vesicles and of HCO3- absorption in microperfused tubules suggested that NHE3 is responsible for most, if not all, apical membrane Na+-H+ exchange in the proximal tubule. The role of NHE3 in mediating proximal tubule HCO3- absorption and formate-dependent Cl- absorption was confirmed by studies in NHE3 null mice. Finally, we cloned and functionally expressed CFEX, an anion transporter expressed on the apical surface of proximal tubule cells and capable of mediating Cl(-)-formate exchange.     

Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter

The NBC1 Na+/HCO3- cotransporter is expressed in many tissues, including kidney and intestinal epithelia. NBC1 mutations cause proximal renal tubular acidosis in humans, consistent with its role in HCO3- absorption in the kidney. In intestinal and colonic epithelia, NBC1 localizes to basolateral membranes and is thought to function in anion secretion. To test the hypothesis that NBC1 plays a role in transepithelial HCO3- secretion in the intestinal tract, null mutant (NBC1-/-) mice were prepared by targeted disruption of its gene (Slc4a4). NBC1-/- mice exhibited severe metabolic acidosis, growth retardation, reduced plasma Na+, hyperal-dosteronism, splenomegaly, abnormal dentition, intestinal obstructions, and death before weaning. Intracellular pH (pH(i)) was not altered in cAMP-stimulated epithelial cells of NBC1-/- cecum, but pH(i) regulation during sodium removal and readdition was impaired. Bioelectric measurements of NBC1-/- colons revealed increased amiloride-sensitive Na+ absorption. In Ringer solution containing both Cl- and HCO3-, the magnitude of cAMP-stimulated anion secretion was normal in NBC1-/- distal colon but increased in proximal colon, with the increase largely supported by enhanced activity of the basolateral NKCC1 Na+-K+-2Cl- cotransporter. Anion substitution studies in which carbonic anhydrase was inhibited and transepithelial anion conductance was limited to HCO3- revealed a sharp decrease in both cAMP-stimulated HCO3- secretion and SITS-sensitive current in NBC1-/- proximal colon. These results are consistent with the known function of NBC1 in HCO3- absorption in the kidney and demonstrate that NBC1 activity is a component of the basolateral mechanisms for HCO3- uptake during cAMP-stimulated anion secretion in the proximal colon.     

Effects of vanadate on water and electrolyte transport in rat jejunum

The effect of vanadate (orthovanadate, VO4-) on water and ion transport was studied in rat jejunum. Water transport was tested by single-pass perfusion in vivo and ion fluxes by the Ussing-chamber technique in vitro. The results suggest that vanadate has two actions on ion and water transport: At low concentrations (10(-4) M) it causes Cl-, Na+ and water secretion by stimulation of adenylate cyclase; At higher concentrations (10(-3) and 10(-2) M) it decreases net absorption of Na+ and Cl- by inhibition of (Na+ + K+)-ATPase.     

Colonic absorption of inorganic ions and volatile fatty acids in the rabbit

Net fluxes of water, Na+, K+, Cl-, HCO3- and volatile fatty acids (VFA) were investigated in three different segments of rabbit colon. Two opposite phenomena occurred: secretion of water and inorganic ions in the oral part of the colon and absorption in the remaining colon; VFA were always absorbed. The movement of cations was closely correlated with those of VFA and Cl-. Results are consistent with the presence of exchange: Na+/H+, K+/H+, in the colon brush border membrane. In fact net absorption of cations and VFA seems linked to the availability of protons. In the absence of net cation transport an additional source of protons may be provided by hydration of luminal CO2. So VFA could enter mucosa by passive diffusion as the undissociated acids.     

Na+,K+ pump and Na+-coupled ion carriers in isolated mammalian kidney epithelial cells: regulation by protein kinase C.

This review updates our current knowledge on the regulation of Na+/H+ exchanger, Na+,K+,Cl- cotransporter, Na+,Pi cotransporter, and Na+,K+ pump in isolated epithelial cells from mammalian kidney by protein kinase C (PKC). In cells derived from different tubule segments, an activator of PKC, 4beta-phorbol 12-myristate 13-acetate (PMA), inhibits apical Na+/H+ exchanger (NHE3), Na+,Pi cotransport, and basolateral Na+,K+ cotransport (NKCCl) and augments Na+,K+ pump. In PMA-treated proximal tubules, activation of Na+,K+ pump probably plays a major role in increased reabsorption of salt and osmotically obliged water. In Madin-Darby canine kidney (MDCK) cells, which are highly abundant with intercalated cells from the collecting duct, PMA completely blocks Na+,K+,Cl- cotransport and decreases the activity of Na+,Pi cotransport by 30-40%. In these cells, agonists of P2 purinoceptors inhibit Na+,K+,Cl- and Na+,Pi cotransport by 50-70% via a PKC-independent pathway. In contrast with MDCK cells, in epithelial cells derived from proximal and distal tubules of the rabbit kidney, Na+,K+,Cl- cotransport is inhibited by PMA but is insensitive to P2 receptor activation. In proximal tubules, PKC-induced inhibition of NHE3 and Na+,Pi cotransporter can be triggered by parathyroid hormone. Both PKC and cAMP signaling contribute to dopaminergic inhibition of NHE3 and Na+,K+ pump. The receptors triggering PKC-mediated activation of Na+,K+ pump remain unknown. Recent data suggest that the PKC signaling system is involved in abnormalities of dopaminergic regulation of renal ion transport in hypertension and in the development of diabetic complications. The physiological and pathophysiological implications of PKC-independent regulation of renal ion transporters by P2 purinoceptors has not yet been examined.     

Electrical properties and fluxes of Na+ and Cl- across lizard intestine

Electrical parameters and unidirectional Na+ and Cl- fluxes were determined in vitro across the duodenum, ileum and colon of lizard (Gallotia galloti). Electrical potential difference (PD) and short circuit current (Isc) were low in the three segments studied, whilst tissue conductance (Gt) was high. A net active transport of Na+ and Cl- was observed in the three segments. Net Na+ absorption was higher across duodenum and ileum than across the colon, while net Cl- absorption was similar in duodenum, ileum and colon. Ouabain virtually abolished Isc, PD and net Na+ and Cl- fluxes in all the segments. Amiloride abolished net Cl- flux in duodenum, ileum and colon, whereas net Na+ flux was abolished in colon but decreased in duodenum and ileum. PD and Isc were not affected by the presence of the diuretic.     

Effect of short-chain fatty acids on cyclic 3',5'-guanosine monophosphate-mediated colonic secretion

Short chain fatty acids (SCFA) prevent and reverse cyclic 3',5'-adenosine monophosphate (cAMP) but not Ca(2+)-mediated Cl- secretion. Mucosal [HCO3-]i has an opposite effect on these secretagogues. We examined whether SCFA and [HCO3-]i affect cyclic 3',5'-guanosine monophosphate (cGMP)-induced secretion. Stripped segments of male Sprague-Dawley rat (Rattus norvegicus) proximal and distal colon, and cultured T84 cells were studied in Using chambers, and pHi and [HCO3-]i were determined. Mucosal [cGMP] was measured in proximal colon. In T84 cells, the increase in Cl- secretion (measured as Isc) induced by mucosal 0.25 microM Escherichia coli heat-stable enterotoxin (STa) was prevented/reversed by bilateral 50 mM Na+ butyrate (71%/73%), acetate (58%/76%), propionate (68%/73%) and (poorly metabolized) isobutyrate (80%/79%). In proximal colon in HCO3- Ringer, basal Cl- secretion was not affected by [HCO3-]i or 25 mM butyrate. Mucosal 0.25 microM STa decreased net Na+ and Cl- absorption. Bilateral but not mucosal 25 mM SCFA reversed STa-induced effects on Na+ absorption and Cl- secretion. Bilateral and mucosal 25 mM SCFA but not [HCO3-]i prevented STa-induced Cl- secretion and increases in mucosal [cGMP]. STa did not produce Cl- secretion in distal colon. It was concluded that SCFA but not [HCO3-]i can prevent and reverse cGMP-induced colonic Cl- secretion.     

Activation of CFTR by ASBT-mediated bile salt absorption

In cholangiocytes, bile salt (BS) uptake via the apical sodium-dependent bile acid transporter (ASBT) may evoke ductular flow by enhancing cAMP-mediated signaling to the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. We considered that ASBT-mediated BS uptake in the distal ileum might also modulate intestinal fluid secretion. Taurocholate (TC) induced a biphasic rise in the short circuit current across ileal tissue, reflecting transepithelial electrogenic ion transport. This response was sensitive to bumetanide and largely abrogated in Cftr-null mice, indicating that it predominantly reflects CFTR-mediated Cl- secretion. The residual response in Cftr-null mice could be attributed to electrogenic ASBT activity, as it matched the TC-coupled absorptive Na+ flux. TC-evoked Cl- secretion required ASBT-mediated TC uptake, because it was blocked by a selective ASBT inhibitor and was restricted to the distal ileum. Suppression of neurotransmitter or prostaglandin release, blocking of the histamine H1 receptor, or pretreatment with 5-hydroxytryptamine did not abrogate the TC response, suggesting that neurocrine or immune mediators of Cl- secretion are not involved. Responses to TC were retained after carbachol treatment and after permeabilization of the basolateral membrane with nystatin, indicating that BS modulate CFTR channel gating rather than the driving force for Cl- exit. TC-induced Cl- secretion was maintained in cGMP-dependent protein kinase II-deficient mice and only partially inhibited by the cAMP-dependent protein kinase inhibitor H89, suggesting a mechanism of CFTR activation different from cAMP or cGMP signaling. We conclude that active BS absorption in the ileum triggers CFTR activation and, consequently, local salt and water secretion, which may serve to prevent intestinal obstruction in the postprandial state.     

Effects of caffeine on transport, metabolism and ultrastructure of isolated rat colon

The effect of caffeine on the transport, metabolism and ultrastructure of the colon were determined. Segments of proximal colon were excised from the anesthetized rat and prepared for radioisotopic tracing of ion transport in the flux chambers or oxidative metabolism in an incubator. Other segments were fixed before or after caffeine administration for electron microscopy. The isolated rat colon actively transported both Na+ and Cl- in the absorptive direction, mucosa to serosa. Serosal addition of 10 mmol/l caffeine abolished the smaller Na+ transport but did not significantly affect the larger Cl- transport. The electrical potential difference and the short-circuit current rose accordingly. Although the oxidation of glucose was inhibited by 35%, caffeine had no significant effect on the oxidation of the fatty acid, butyric acid. Comparable metabolic responses were obtained using the isolated terminal ileum of the rat. Neither the height nor the density of the microvilli in the proximal colon were affected significantly by caffeine. It may be concluded that caffeine, unlike theophylline, effectively preserves the normal absorptive condition of the colon. Thus, caffeine may have actions other than inhibition of phosphodiesterase in the distal intestine.     

Variation in amino acid transport along the rabbit small intestine. Mutual jejunal carriers of leucine and lysine.

The jejuno-ileal variation of amino and imino acid transport across the brush-border membrane of intact rabbit small intestine was studied. For the amino acids tested--beta-alanine, leucine, lysine, MeAIB, proline--and for D-glucose, the rates of transport at constant concentrations increase from very low values in the proximal jejunum to maximum values in the most distal 30 cm of the ileum. The apparent affinity constant for jejunal taurine transport is identical to that of the distal ileum, while the jejunal transport capacity is less than half. In the jejunum, as in the distal ileum, leucine and lysine share both sodium-dependent and sodium-independent carriers. Approx. 50% of the quantitative difference in transport capacity is accounted for by the absence of the beta-alanine carrier in the jejunum. These data indicate that the gradients of transport along the small intestine reflect gradients of transport capacities rather than affinities. In comparison with hamster, man and rat, the rabbit seems unique with respect to the location of transport maximum and the steepness of the gradient along the intestine.