Some major transport mechanisms of insect absorptive epithelia

1. After hormonal stimulation, fluid reabsorption (JV) in locust hindgut from the KCl-rich, low-Na primary urine is driven primarily by an unusual mucosal electrogenic Cl- pump (JCl). 2. Cyclic-AMP increases JCl and also mucosal K+ and basolateral Cl- conductances, so that KCl absorption exceeds that of Na+ in rectum but not ileum. 3. Mucosal entry of Na+ occurs by exchange for NH4+ (H+), by cotransport with some neutral amino acids, and through putative channels. 4. However, transport of proline, the predominant organic substrate, is largely Na-independent and drives a sizable component of Jv in rectal but not ileal segments. 5. There is evidence for hormonal control of Na+ reabsorption in ileum but not rectum.     

TNF-alpha down-regulates the Na+-K+ ATPase and the Na+-K+-2Cl-cotransporter in the rat colon via PGE2

TNF-alpha is believed to play a pivotal role in the pathogenesis of inflammatory bowel diseases which have diarrhea as one of their symptoms. This work studies the effect of the cytokine on electrolyte and water movements in the rat distal colon using an intestinal perfusion technique and attempts to determine its underlying mechanism of action. TNF-alpha inhibited net water and chloride absorption, down-regulated in both surface and crypt colonocytes the Na+-K+-2Cl- cotransporter, and reduced the protein expression and activity of the Na+-K+ ATPase. Indomethacin up-regulated the pump and the cotransporter in surface cells but not in crypt cells, and in its presence, TNF-alpha could not exert its effect, suggesting an involvement of PGE2 in the cytokine action. The effect of TNF-alpha on the pump and symporter was studied also in cultured Caco-2 cells in isolation of the effect of other cells and tissues, to test whether the cytokine acts directly on intestinal cells. In these cells, TNF-alpha and PGE2 had a similar effect on the pump expression and activity as that observed in crypt cells but were without any effect on the Na+-K+-2Cl- cotransporter. It was concluded that the effect of the cytokine on colonocytes is mediated via PGE2. By inhibiting the Na+-K+ ATPase, it reduces the Na+ gradient needed for NaCl absorption, and by down-regulating the expression of the Na+-K+-2Cl- symporter, it reduces basolateral Cl- entry and luminal Cl- secretion. The inhibitory effect on absorption is more significant than the inhibitory effect on secretion resulting in a decrease in net electrolyte uptake and consequently in more water retention in the lumen.     

Intestinal water absorption from select carbohydrate solutions in humans.

Eight men positioned a triple-lumen tube in the duodenojejunum. By use of segmental perfusion, 2, 4, 6, or 8% solutions of glucose (111-444 mM), sucrose (55-233 mM), a maltodextrin [17-67 mM, avg. chain length = 7 glucose units (7G)], or a corn syrup solid [40-160 mM, avg. chain length = 3 glucose units (3G)] were perfused at 15 ml/min for 70 min after a 30-min equilibration period. All solutions were made isotonic with NaCl, except 6 and 8% glucose solutions, which were hypertonic. An isotonic NaCl solution was perfused as control. Water absorption (range: 9-15 ml.h-1.cm-1) did not differ for the 2, 4, and 6% CHO solutions but was greater (P < 0.05) than absorption from control (3.0 +/- 2.2 ml.h-1.cm-1). The 8% glucose and 3G solutions reduced (P < 0.05) net water flux compared with their 2, 4, and 6% solutions, but 8% sucrose and 8% 7G solutions promoted water absorption equivalent to lower CHO concentrations. Water absorption was independent of [Na+] in the original solution. In the test segment, 1) Na+ flux correlated with net water flux (r = 0.72, P < 0.01), K+ (r = 0.78, P < 0.01), and [Na+] (r = 0.68, P < 0.001); 2) Na+ absorption occurred at luminal [Na+] as low as 50 mM; 3) glucose transport increased linearly over the luminal concentration range of 40-180 mM; and 4) net water flux was similar over a range of glucose-to-Na+ concentration ratios of 0.4:1 to 3.5:1.(ABSTRACT TRUNCATED AT 250 WORDS)     

An analogue computer simulation of cloacal resorption of salt and water from ureteral urine in birds

The transmural flow of NaCl and water occurring during the retrograde flow of ureteral urine into the coprodeum and large intestine of birds has been simulated by analogue computation. The purpose was to estimate whether a fraction of the urine (water) which in the dehydrated state is hyperosmotic to plasma can, in spite of this, be absorbed from the narrow space between the epithelium and the central faeces core. The values of urine flow, urine osmolality, osmotic permeability, net NaCl absorption rate, and solute-linked water flow determined by in vivo perfusion studies in the domestic fowl were used in the calculation. The cloacal sojourn of ureteral urine was found to result in a net water gain but at the expense of a hyperosmotic NaCl absorption. The model was further used to evaluate the quantitative influence of the system's parameters upon the fractional water absorption. This was found very sensitive to the urine osmolality, moderately sensitive to the urine flow and NaCl absorption rate and almost unaffected by the osmotic permeability of the coprodeum and large intestine within a reasonable physiological range. The change of the epithelial transport parameters from the normally hydrated to the dehydrated state resulted in a marked increase in water absorption.     

PGE2 exerts dose-dependent opposite effects on net water and chloride absorption from the rat colon

This work investigated the effect of different doses of PGE2 on net water and Cl- absorption from the rat colon, using an in situ perfusion technique. PGE2 exerted opposite effects at different concentrations. Net water and Cl- absorption was significantly reduced at low doses with a minimum at 0.4 microg/100g BW, and significantly elevated at high doses with an observed maximal effect at 21 microg/100g BW. At low doses, PGE2 increased in superficial cells, the activity of the Na+-K+ ATPase and the protein expression of the Na+K+2Cl- cotransporter, but reduced them in crypt cells. Thus, the reduction in net water and Cl- absorption was ascribed to an increase in secretion by surface cells that masked absorptive processes. At high doses, PGE2 increased significantly the activity of the Na+-K+ ATPase in superficial cells only, and was without any effect on the protein expression of the cotransporter and the pump in both surface and crypt cells. The observed increase in net water and Cl- absorption was attributed in this case to an increase in absorptive processes with no effect on secretion.     

PGE2 reduces net water and chloride absorption from the rat colon by targeting the Na+/H+ exchanger and the Na+ K+ 2Cl- cotransporter

An effect of PGE2 on water and chloride absorption was already established in a previous work. This study is an attempt to find the mechanism of action of the prostaglandin by investigating the involvement of three major transporters namely the Na+ -K+ ATPase, the Na+/H+ exchanger and the Na+ K+ 2Cl- cotransporter. Rats were injected with PGE2 and 15 min later, the colon was perfused in situ with Krebs Ringer buffer, and net water and chloride absorption were determined. When the involvement of the cotransporter and/or the exchanger was investigated, animals were injected with, respectively, furosemide and amiloride 10 min before PGE2. Superficial and crypt colonocytes were then isolated and the protein expression of the Na+ -K+ ATPase and the Na+ K+ 2Cl- was determined by western blot analysis. The effect of PGE2 on the pump activity in presence or absence of the transporters' inhibitors was also studied. PGE2 decreased net water and chloride absorption from the colon, increased the Na+ -K+ ATPase activity in superficial cells and reduced it in crypt cells. The prostaglandin was found to stimulate secretion in superficial cells by targeting the Na+ K+ 2Cl- symporter, and reduce absorption in crypt cells by targeting the Na+/H+ antiporter. Changes in the activity of the pump are secondary to changes in the activity of the other transporters.     

Involvement of the cytoskeleton in the effect of PGE2 on ion transport in the rat distal colon

This work aimed at studying the effect of PGE2 on water and chloride absorption from the rat distal colon and at investigating the involvement of the cytoskeleton in the modulation of colonic transporters. PGE2 increased significantly net water and chloride absorption. It increased also the activity of the Na+K+-ATPase and the expression of the Na+K+2Cl- cotransporter. The increase in pump activity was ascribed to its phosphorylation by PKA or PKC when activated upon binding of PGE2 to its receptors, and was deemed responsible for the increase in Cl- absorption. Cytochalasin B (CytoB), a disrupter of microfilaments, decreased net water and chloride absorption in presence or absence of PGE2. Furthermore it down-regulated both pump and cotransporter, and lowered Na+K+-ATPase activity. It was suggested that an intact actin cytoskeleton is required for the basal and the PGE2-elicited trafficking of both transporters. On the other hand, colchicine, an inhibitor of microtubule polymerization, had no effect on the absorption of water and chloride but abrogated the stimulatory effect of PGE2. Colchicine exerted a similar effect to that of cytochlasin on the expression of both pump and cotransporter in presence or absence of PGE2 except for the basal activity of the pump which was not altered by microtubule disruption. It was concluded that both microfilament and microtubular networks are involved in the basal and PGE2-elicited increase in colonic ion absorption.     

Effect of hypophysectomy on absorption of inorganic phosphate by the eel intestine

Hypophysectomy of freshwater-adapted eels resulted in a marked reduction in net absorption of PO4(3-) in the non-stripped and non-everted intestine. Stanniectomy was without effect on net movements of water and electrolytes in this isolated eel preparation. Repeated injections of eel calcitonin into the eel, kept either in deionized water or 10 mM CaCl2, had no effect on net absorption of water and electrolytes, including Ca2+ and PO4(3-). In the stripped and everted intestine, the net PO4(3-) absorption was significantly greater in the fed eel than in the starved fish. Hypophysectomy of the fed eel resulted in a significant reduction, not only in PO4(3-) absorption, but also in absorption of water and other electrolytes. It is suggested that pituitary hormone is involved in the intestinal PO4(3-) absorption of the eel.     

Protein digestion and ion concentrations in rainbow trout (Salmo gairdnerii Rich.) digestive tract in sea- and fresh water

• 1.1. Rainbow trout maintained in fresh water or Actapted to sea-water for 24 hr were fed casein-based dry diet. After feeding, fish were kept in fresh water (FW) or transferred to artificial sea-water (SW) and sacrificed after 10 or 20 hr.
• 2.2. The digestive tract was separated into five parts: stomach, pyloric caeca region, middle intestine and two equal lengths of rectum.
• 3.3. The content of these parts was analysed for ions Na⁺, K⁺, Cl⁻, Mg²⁺ and for free, peptide and total amino acids.
• 4.4. In the fish stomach all ions, with the exception of Ca²⁺, indicate drinking of sea-water. In the pyloric caeca region Na⁺ appears to be efficiently absorbed in SW fish but influxed in FW fish. In the rectum of SW fish K⁺ appears to be reabsorbed but Na⁺ concentrated in faeces.
• 5.5. Free amino acid concentrations were always higher in gut lumen of SW than in FW fish in respect to time after feeding and portion of intestinal content. Free amino acids constitute at most 7.4–8.7% of total amino acids in the content of pyloric caeca region.
• 6.6. Peptide amino acids, being mostly di-, tri- and tetra-peptides, increased in stomach content from 14.7 to 28.4% of the total, from 6 to 10 hr after a meal in SW fish. Peptide amino acids constituted 80.3–89.0% of total amino acids in intestinal content of the pyloric caeca region. These peptide portions decreased in the mid-intestine (47.5–52.5%) and increased again in the rectum (73.6–76.0%).
• 7.7. It was concluded that in rainbow trout fed in both sea- or fresh water, ion concentrations do not seem to interfere with protein digestion and nutrient absorption in alimentary tract.

     

Drinking and osmoregulation in the mangrove crab Ucides cordatus following exposure to benzene

In benzene-exposed Ucides cordatus acclimated for 96 h to 9 and 34 per thousand SW, haemolymph, urine and gastric juice are isosmotic with each other, but differ significantly in osmolality from external media. In both salinities, under benzene action, urine K+ excretion and calcium absorption are increased significantly, whereas Na+ absorption and Mg2+ excretion show U/B ratios similar to control values. In 9 per thousand SW, some ionic exchanges via benzene-exposed gills are possibly hastened. Benzene exposure decreases significantly branchial chamber water osmolality, [Na+] and [K+], whereas [Ca2+] and [Mg2+] are unaffected. However, faster medium exchange presumably occurs in 34 per thousand SW, both crab groups show branchial chamber water osmotic and ionic concentrations similar to surrounding medium. Benzene exposure unaffected gastric juice composition. In both media, [Ca2+] and [Mg2] accumulate several times higher than surrounding media, and [Na+] and [K+] are significantly hypo-ionic to haemolymph. Na+ and K+ G/H ratios are lower in crabs acclimated to 34 per thousand SW than in crabs acclimated to 9 per thousand SW. Drinking rates are enhanced by benzene exposure and are higher at 34 per thousand SW than in seawater isosmotic with the haemolymph (26 per thousand SW). Benzene exposure affects significantly osmoregulatory capability, slowing haemolymph dilution after transfer to clean 9 per thousand SW. Lower haemolymph dilution rate accounts for higher osmolality, but 48 h after transfer there is no recovery like in control crabs. Haemolymph transfusion experiments suggest an interaction among effects of benzene and hormonal factors, possibly on water influx.     

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.     

Uncoupled basal sodium absorption and chloride secretion in prairie dog (Cynomys ludovicianus) gallbladder.

1. Prairie dog gallbladders mounted in a Ussing-type chamber and bathed with symmetrical Ringer's solutions exhibited a transepithelial resistance (Rt) of 51 +/- 5 omega cm2, a lumen negative potential difference (Vms) of 11.5 +/- 0.7 mV and a short-circuit current (Isc) of 6.9 +/- 0.3 microEq/hr/cm2. 2. Radioisotopic ion flux experiments revealed that the basal Isc of 6.9 +/- 0.3 microEq/hr/cm2 was mostly accounted for by net Na+ absorption of 3.2 +/- 0.5 microEq/hr/cm2 and net Cl- secretion of 2.9 +/- 0.3 microEq/hr/cm2. 3. In HCO3- free Ringer's, net Na+ flux was virtually abolished, net Cl- flux decreased by 50% and Isc was reduced by 77%. 4. 10(-3) M mucosal amiloride and DIDS reduced Isc by 28 and 24%, respectively. 5. Mucosal NaCl diffusion potentials indicated that the paracellular pathway was cation selective. 6. Thin section electron micrographs showed a single cell population in this epithelium suggesting that net Na+ absorption and Cl- secretion may emerge from the same cells. 7. We conclude that prairie dog gallbladder epithelium is an electrogenic tissue and, in contrast to gallbladders of most other species, simultaneously but independently absorbs Na+ and secretes Cl-.     

Human placental brush-border membrane Na(+)-pantothenate cotransport.

Membrane transport pathways for transplacental transfer of the water-soluble vitamin pantothenate were investigated by assessing the possible presence of a Na(+)-pantothenate cotransport mechanism in the maternal facing membrane of human placental epithelial cells. The presence of Na(+)-pantothenate cotransport was determined from radiolabeled tracer flux measurements of pantothenate uptake using preparations of purified brush-border membrane vesicles. Compared with other cations the imposition of an inward Na+ gradient stimulated vesicle uptake of pantothenate to levels approximately 40-fold greater than those observed at equilibrium. The observed stimulation of pantothenate uptake was not the result of indirect electrostatic coupling to an inside positive Na+ diffusion potential. In the absence of Na+ and pantothenate concentration gradients an inside negative voltage difference induced a Na(+)-dependent net influx of pantothenate, suggesting the presence of an electrogenic Na(+)-pantothenate cotransport mechanism. The effect of biotin on the kinetics of Na(+)-dependent pantothenate uptake and the effect of pantothenate on the kinetics of Na(+)-dependent biotin uptake suggested that placental absorption of biotin and pantothenate from the maternal circulation occurs by a common Na+ cotransport mechanism in apical brush-border membrane.     

The mechanism underlying the laxative properties of Parsley extract

Parsley has been claimed in folk medicine to possess laxative properties attributed to the presence therein of some volatile oils that are more concentrated in seeds than in stems or leaves. The advocated physiological effect of parsley, does not have, however, any proven scientific background and relies mainly on simple observations and empirical information. This work aims at providing the scientific evidence that would confirm or reject the claimed laxative role of parsley, and at determining its mechanism of action if present. A perfusion technique was used to measure the net fluid absorption from the rat colon. The addition of an aqueous extract of parsley seeds to the perfusion buffer, and the omission of sodium, both reduced significantly net water absorption from the colon, as compared to the control. Parsley, added to a sodium-free buffer did not lead to any further significant change in water absorption as compared to parsley alone inferring that with parsley sodium absorption was already inhibited. Since K+ and Cl- secretion depends on the activity of the NaKCl2 transporter, the latter was inhibited with furosemide which increased significantly net water absorption. When parsley and furosemide were added together, net water absorption was significantly higher than with parsley alone and significantly lower than with furosemide alone. In addition, parsley extract was shown to inhibit the in vitro activity of the Na+-K+ATPase in a colon homogenate and the activity of a partially purified dog kidney ATPase. The results suggest that parsley acts by, inhibiting sodium and consequently water absorption through an inhibition of the Na+-K+ pump, and by stimulating the NaKCl, transporter and increasing electrolyte and water secretion.     

Bacterial pneumonia stimulates macromolecule secretion and ion and water fluxes in sheep trachea

In vivo instillation of Pasteurella haemolytica (greater than or equal to 10(7) colony-forming units/kg) into a lobar bronchus of sheep produced bacterial pneumonia by 7 days postinoculation. Infection was verified bacteriologically and histologically. Macromolecule secretion and ion and water fluxes were subsequently measured in tracheal tissues in vitro and were compared with values from sham-infected sheep. Macromolecules were radiolabeled with 35SO4 and [3H]threonine, and we measured the secretion of macromolecule-bound radiolabel onto the mucosa. Unidirectional fluxes of Cl-, Na+, and water were measured with radioactive tracers under open-circuit and short-circuit conditions. Lung infection increased basal secretion of bound 35SO4 (by 189%) and bound [3H]-threonine (by 110%). It significantly increased net Na+ absorption under open- and short-circuit conditions and induced open-circuit net absorption of Cl- and water (16 +/- 29 microliters X cm-2 X h-1). These changes were associated with specific recruitment of neutrophils and elevated levels of arachidonate metabolites (thromboxane B2 and leukotriene B4) in the airways. Thus the bacterial pneumonia-induced changes in tracheal mucus secretion may be the result of airway inflammation.     

Studies on the mechanism of Escherichia coli heat-stable enterotoxin-induced diarrhoea in mice

The unidirectional fluxes of Na+, Cl- and Ca2+ and activities of calmodulin in the intestinal microvillar core were studied in Escherichia coli heat-stable enterotoxin-treated mice. There was net secretion of Na+ and Cl- in toxin-treated animals, while in control animals there was net absorption of these ions. In both control and experimental animals, there was net absorption of Ca2+; however, the absorption was significantly higher (P less than 0.01) in experimental animals when compared to controls. In the presence of Ca2+-ionophore, there was a net secretion of Na+ and Cl- in controls, while the Ca2+-ionophore could not cause any change in the fluxes of these ions in experimental animals. The activity of calmodulin was significantly higher (P less than 0.01) in experimental animals. Verapamil, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, reversed the effects of Ca2+-ionophore and heat-stable enterotoxin. These studies demonstrate that the toxin acts through Ca2+-calmodulin, and secretion of Na+ and Cl- in experimental animals is due to an increase in calcium absorption and an increase in calmodulin activity in the intestinal microvillar core.     

Application of the Na+ recirculation theory to ion coupled water transport in low- and high resistance osmoregulatory epithelia

The theory of Na+ recirculation for isosmotic fluid absorption follows logically from Hertz's convection-diffusion equation applied to the exit of water and solutes from the lateral intercellular space. Experimental evidence is discussed indicating Na+ recirculation based upon the following approaches: (i) An isotope tracer method in small intestine. Simultaneous measurement of water flow and ion transport in toad skin epithelium demonstrating, (ii) occasional hyposmotic absorbates, and (iii) reduced fluid absorption in the presence of serosal bumetanide. (iv) Studies of the metabolic cost of net Na+ absorption demonstrating an efficiency that is lower than the 18 Na+ per O2 consumed given by the stoichiometry of the Na+/K+-pump. Mathematical modeling predicts a significant range of observations such as isosmotic transport, hyposmotic transport, solvent drag, anomalous solvent drag, the residual hydraulic permeability in proximal tubule of AQP1(-/-) mice, the adverse relationship between hydraulic permeability and the concentration difference needed to reverse transepithelial water flow, and in a non-contradictory way the wide range of metabolic efficiencies from above to below 18 Na+/O2. Certain types of observations are poorly or not at all reproduced by the model. It is discussed that such lack of agreement between model and experiment is due to cellular regulations of ion permeabilities that are not incorporated in the modeling. Clarification of these problems requires further experimental studies.     

The electrical potential difference, short circuit current and Na+ and Cl- transport across different segments of sheep colon

1. The electrical potential difference (pd) and short circuit current (Isc) across the sheep colon descendens was significantly higher than across the sheep colon ascendens. 2. The ion equivalent of the Isc and the net Na+ transport from the mucosal (m) to the serosal (s) side of the short-circuited sheep colon descendens were identical, while the net Na+ transport across the colon ascendens exceeded the ion equivalent of the Isc. 3. There was a net m-s Cl- transport across both short-circuited colon segments, indicating that Cl-, like Na+, is absorbed by active transport. 4. The results suggest that active Na+ transport across the sheep colon descendens occurs entirely by an electrogenic mechanism, whereas active Na+ transport across the sheep colon descendens occurs entirely by an electrogenic mechanism, whereas active Na+ transport across sheep colon ascendens probably occurs by both an electrogenic and an electrically silent mechanism.     

Ionic conductance pathways in the mouse medullary thick ascending limb of Henle. The paracellular pathway and electrogenic Cl- absorption

Net Cl- absorption in the mouse medullary thick ascending limb of Henle (mTALH) involves a furosemide-sensitive Na+:K+:2 Cl- apical membrane symport mechanism for salt entry into cells, which occurs in parallel with a Ba++-sensitive apical K+ conductance. The present studies, using the in vitro microperfused mouse mTALH, assessed the concentration dependence of blockade of this apical membrane K+-conductive pathway by Ba++ to provide estimates of the magnitudes of the transcellular (Gc) and paracellular (Gs) electrical conductances (millisiemens per square centimeter). These studies also evaluated the effects of luminal hypertonicity produced by urea on the paracellular electrical conductance, the electrical Na+/Cl- permselectivity ratio, and the morphology of in vitro mTALH segments exposed to peritubular antidiuretic hormone (ADH). Increasing luminal Ba++ concentrations, in the absence of luminal K+, produced a progressive reduction in the transcellular conductance that was maximal at 20 mM Ba++. The Ba++-sensitive transcellular conductance in the presence of ADH was 61.8 +/- 1.7 mS/cm2, or approximately 65% of the total transepithelial conductance. In phenomenological terms, the luminal Ba++-dependent blockade of the transcellular conductance exhibited negative cooperativity. The transepithelial osmotic gradient produced by luminal urea produced blebs on apical surfaces, a striking increase in shunt conductance, and a decrease in the shunt Na+/Cl- permselectivity (PNa/PCl), which approached that of free solution. The transepithelial conductance obtained with luminal 800 mM urea, 20 mM Ba++, and 0 K+ was 950 +/- 150 mS/cm2 and provided an estimate of the maximal diffusion resistance of intercellular spaces, exclusive of junctional complexes. The calculated range for junctional dilution voltages owing to interspace salt accumulation during ADH-dependent net NaCl absorption was 0.7-1.1 mV. Since the Ve accompanying ADH-dependent net NaCl absorption is 10 mV, lumen positive, virtually all of the spontaneous transepithelial voltage in the mouse mTALH is due to transcellular transport processes. Finally, we developed a series of expressions in which the ratio of net Cl- absorption to paracellular Na+ absorption could be expressed in terms of a series of electrical variables. Specifically, an analysis of paired measurement of PNa/PCl and Gs was in agreement with an electroneutral Na+:K+:2 Cl- apical entry step. Thus, for net NaCl absorption, approximately 50% of Na+ was absorbed via a paracellular route.     

Influence of centrally administered somatostatin and two related peptides on intestinal absorption of water and electrolytes in conscious dogs

The effects of intracerebroventricular (ICV) administration of somatostatin (SRIF) and two related peptides, anti SRIF and SMS 201-995, on jejunal fluxes of water, Na+ and K+ were investigated in dogs prepared with a Thiry-Vella (TV) loop. Intestinal transport in the TV loop and concomitant transit time were also measured during infusion (2 mg/min) of an isotonic electrolyte solution and phenol-red bolus injections. Basal net water absorption was reduced significantly (p less than 0.01) over periods of 2 to 5 hr and in a dose-related manner, with ICV administrations of SRIF (5 to 100 ng/kg); doses of SRIF, 5 to 25 times higher but administered IV, were inactive. Similar reductions in the net fluxes of water, Na+ and K+ were observed over 2 to 5 hr following ICV administration of a putative somatostatin antagonist and SMS 201-995 at doses of 100 ng/kg. Neither metoclopramide (1 mg/kg), phentolamine (0.1 mg/kg) nor methysergide (0.2 mg/kg) given IV were able to antagonize the effects of centrally administered SRIF (100 ng/kg) on intestinal fluxes. In contrast, the effects of SRIF were abolished completely by naloxone (0.2 mg/kg) but not methyl-naloxone (0.3 mg/kg) given systemically. It is concluded that somatostatin and the two related peptides act centrally to reduce jejunal absorption of water and electrolytes. The effects of SRIF appear to be related to opiate receptors, possible involving central nerve pathways which utilize opiate-like transmitters.