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M G Raeder

Publications and source records attributed to M G Raeder.

33 records · Page 2Linked to original sources
PubMed1990

Colchicine blocks the effects of secretin on bile duct cell tubulovesicles and plasma membrane geometry and impairs ductular HCO3- secretion in the pig.

Secretin causes the bile duct cells to secrete HCO3-. To examine whether the transformation of duct cell ultrastructure that follows secretin stimulation depends on microtubules and is important for ductular HCO3- secretion, we examined the effect of colchicine on ductular HCO3- secretion and on the morphology of cells lining bile ductules of anaesthetized pigs. Colchicine blocked secretin-dependent cytoplasmic clearance of tubulovesicles and prevented expansion of the basolateral plasma membrane in duct cells and reduced the ductular HCO3- secretory response from 132 +/- 25 mumol min-1 to 97 +/- 14 mumol min-1. In contrast, lumicolchicine did not affect secretin-dependent tubulovesicle clearance or plasma membrane geometry or ductular HCO3- secretion. Accordingly, secretin-dependent cytoplasmic clearance of tubulovesicles in bile duct cells appears to depend on microtubules and to be important for ductular HCO3- secretion.

Animals↗
PubMed1988

Secretin empties bile duct cell cytoplasm of vesicles when it initiates ductular HCO3- secretion in the pig.

To determine whether secretin has any effect on bile duct cell ultrastructure, bile duct cells from liver biopsy specimens of pigs were analyzed morphometrically. During secretory rest, bile duct cell cytoplasmic vesicles totaled 96 (84-103) arbitrary units per cell volume (U). Secretin increased bile HCO3- secretion from 9 mumol/min (range 6-15) to 131 mumol/min (range 118-200) and lowered the bile duct cell vesicles to 5 U (range 3-9). Acute elevation of arterial PCO2 to 10.9 kPa (range 10.2-11.1) doubled vesicle number in resting duct cells and augmented the secretory response to secretin. At high arterial PCO2, secretin cleared the duct cell cytoplasm of vesicles and more than doubled the basolateral plasma membrane surface area. Taurocholate-induced canalicular choleresis, in contrast, did not alter duct cell morphology. It is concluded that secretin clears the bile duct cell cytoplasm of vesicles as it initiates ductular HCO3- secretion, possibly through causing exocytotic insertion of vesicle material into the basolateral plasma membrane.

Animals↗
PubMed1988

Effects of arterial pH and carbon dioxide on pancreatic exocrine H+/HCO3- secretion and secretin-dependent translocation of cytoplasmic vesicles in pancreatic duct cells.

To elucidate why arterial pH and carbon dioxide (PaCO2) modify the pancreatic H+/HCO3- secretory response to secretin stimulation, experiments were performed on anaesthetized pigs, recording the effects of arterial pH and PaCO2 on exocrine H+/HCO3- secretion and on morphology of pancreatic duct cells. Duct cells contained numerous cytoplasmic vesicles at secretory rest. Their number more than doubled during elevation of PaCO2 from 5.5 to 11.0 kPa. At arterial pH 7.40, maximal secretin stimulation cleared the cytoplasm of duct cells of more than 90% of the vesicles. At high PaCO2, this was accompanied by doubling the basolateral plasma membrane area and a 30% higher secretion rate than at PaCO2 5.5 kPa. Lowering arterial pH to 7.0 more than halved the secretin-induced vesicle clearance of duct-cell cytoplasm as well as exocrine H+/HCO3- secretion and abolished the secretin-dependent basolateral membrane area changes. Supramaximal secretin stimulation did not reverse the inhibitory effect of severe metabolic acidosis on secretion. It is concluded that PaCO2 and arterial pH may modify the secretory response to secretin through determining the incorporation of cytoplasmic vesicle material into the basolateral plasma membrane of duct cells.

Animals↗
PubMed1988

Effects of bumetanide on bile flow in the pig.

This study was performed on 12 anaesthetized pigs in order to examine the effect of the 'loop' diuretic bumetanide (inhibitor of Na,K,Cl-co-transport) on ductular bile secretion. It has previously been shown that administration of furosemide (a less potent 'loop' diuretic) to dogs and rats increases bile flow due to inhibition of ductular reabsorption of electrolytes and water. In group I (n = 6) bumetanide (median biliary concentration: 8.4 x 10(-3) mol l-1) increased bile flow and biliary concentration of HCO3 by 200% (116-320) and 50% (26-96), respectively. Biliary concentration of Cl was significantly decreased by 6% (2-12) following administration of bumetanide. In group II (n = 6) bile secretion was measured during secretin infusion (3 CU kg b. wt h-1) in the arterial pH range of 7.40-7.00, both before and after bumetanide administration in each animal. Bumetanide (median biliary concentration: 2.7 x 10(-3) mol I-1) did not significantly alter biliary secretion of water, HCO3, Na, K or Cl. Bile acid secretion was reduced by 30% from 43 (28-55) to 30 (17-41) mumol min-1 (P less than 0.05) while hepatic venous concentration of bile acids was raised by 90% (54-126) from 184 (113-309) to 350 (229-502) mumol l-1 (P less than 0.05) at slightly increased hepatic blood flow. Hepatic venous serum concentration of bumetanide was 4.8 (2.1-7.4) x 10(-4) mol l-1 (unbound fraction).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Importance of carbonic anhydrase for canalicular and ductular choleresis in the pig.

To assess the importance of carbonic anhydrase (CA) for canalicular and ductular choleresis, the effect of acetazolamide on bile secretion was measured in three experimental groups of anaesthetized pigs. CA activity in liver homogenate was 46 (43-54) U g-1 wet weight, 150 mg kg-1 b.w. acetazolamide completely abolished the CA activity. Acetazolamide reduced bile HCO3- secretion in six secretin infused, bile-acid depleted pigs by 67 (58-71)% at arterial pH 7.41 (7.38-7.46). By contrast, acetazolamide did not affect HCO3- secretion in six Na-taurocholate (TCA) infused pigs in the absence of secretin stimulation. Acetazolamide reduced ursodeoxycholic-acid- (UDCA) dependent HCO3- secretion by 24 (11-38)% in six other pigs in the absence of secretin stimulation. Histochemical examination using modifications of Hansson's method showed strong reaction in bile ductules and weaker reaction in peripheral zones of liver lobules. Because acetazolamide impairs HCO3- secretion from cells sustaining high rates of H+/HCO3- transport, it is suggested that high rates of H+/HCO3- transport are confined to bile ductules under conditions of secretin- and UDCA-induced choleresis.

Acetazolamide↗
PubMed1987

The effect of amiloride on biliary HCO3- secretion in the anaesthetized pig.

The present study was performed on 29 anaesthetized pigs and shows that the bile acid ursodeoxycholic acid (UDCA) produces a flow of bile rich in HCO3- compared with taurocholic acid (TCA). The slope relating biliary HCO3- secretion to bile acid secretion was 0.59 (0.44-0.82) and 0.33 (0.29-0.38) during venous infusion of UDCA and TCA, respectively. We next wanted to evaluate the importance of Na+/H+ ion exchange for biliary HCO3- secretion. High doses of amiloride were employed in order to impair the hepatic Na+/H+ ion exchanger. It was reasoned that any reduction in H+ efflux through the hepatic Na+/H+ ion exchanger involved in causing biliary HCO3- secretion would be translated into an equimolar fall in biliary HCO3- secretion. We found that amiloride (2.0 X 10(-4) mol l-1 plasma) reduced UDCA-dependent canalicular HCO3- secretion by 26 (14-35)% without concurrently reducing bile acid secretion. Amiloride (2.9 X 10(-4) mol l-1 plasma) did not significantly reduce secretin-dependent ductular HCO3- secretion. In this group of animals amiloride reduced bile acid secretion by 13 (5-22)%. It is concluded that Na+/H+ ion exchanger is essential for UDCA-dependent canalicular HCO3- secretion, but not for secretin-dependent ductular HCO3- secretion.

Amiloride↗
PubMed1987

Localization of K-NPPase and Li+ secretion in the exocrine pancreas of the pig.

To study the mode of transepithelial Na+ transport into pancreatic ducts during secretin-dependent NaHCO3 secretion, Na, K-ATPase was first localized within the exocrine pancreas of the pig using a cytochemical reaction for K-dependent p-nitrophenylphosphatase (K-NPPase). K-NPPase staining was confined to the lateral cell membrane bordering the intercellular spaces between ductal cells, negating the possibility of primary active, transcellular Na+ transport into pancreatic ducts. To assess how transepithelial Na+ transport may be coupled to HCO-3 secretion, net flux of Li+ into pancreatic juice was measured following intravenous systemic Li+ loading of 12 secretin infused, anaesthetized pigs. At plasma Li+ 32 (23-35) mmol l-1, Li+ displaced Na+ as accompanying cation to secreted HCO-3, and Li+/Na+ in pancreatic juice matched Li+/Na+ in arterial plasma. During superimposed inhibition of pancreatic water flux by hyperglycaemia, Li+ and Na+ were both transported against a transepithelial concentration gradient. Li+ reduced pancreatic HCO-3 secretion rate by 14 (-2 to -20)%, as well as Na,K-ATPase activity in a separate in vitro assay. The finding that Li+ substituted for Na+ in the secretion even during reduced osmotic water flow suggests that Na+ and Li+ are transported together with secreted HCO-3 into pancreatic juice by an electrogenic mechanism in addition to solvent drag and diffusion.

4-Nitrophenylphosphatase↗
PubMed1987

Ultrastructure of pancreatic duct cells at secretory rest and during secretin-dependent NaHCO3 secretion.

The study was undertaken to identify possible ultrastructural changes occurring in pancreatic duct cells in relation to secretin-dependent NaHCO3 secretion, Pancreatic biopsies were obtained for examination, following in situ glutaraldehyde fixation from four groups of anaesthetized, young pigs. In the resting state, pancreatic duct cell cytoplasm was found to contain multiple vesicles of approximately 0.2 micron diameter. Elevation of systemic arterial PCO2 to 11.1 (10.6-11.6) kPa increased the number of vesicles per unit volume of resting cells by approximately 250%. During secretin-dependent NaHCO3 secretion, the duct cell cytoplasm was devoid of vesicles. Following cessation of secretin-dependent NaHCO3 secretion, cytoplasmic vesicles reappeared. The observed changes in the population of cytoplasmic vesicles in pancreatic duct cells may be causally related to the exocrine secretion of NaHCO3.

Animals↗
PubMed1987

Effect of arterial pH and PCO2 on biliary HCO3- secretion in the pig.

The purpose of the present study was to examine the effect of changes in arterial pH and PCO2 on biliary HCO3- secretion. This was done in order to further characterize the various ion transport mechanisms considered responsible for biliary HCO3- secretion in the pig. Experiments were performed on two groups of six pigs. In both groups arterial pH was varied in steps from pH 7.40 to 7.00, both at PCO2 5.5 kPa and PCO2 10 kPa. In group I (n = 6), data were obtained on the effect of arterial pH and PCO2 on ductular HCO3- secretion in bile acid depleted (cholestyramine pretreated), secretin-infused pigs. In group II (n = 6), the effect of pH and PCO2 on canalicular HCO3- secretion was studied in ursodeoxycholic acid (UDCA)-infused pigs (3 mumol min-1 kg-1 body wt). In group I, biliary HCO3- secretion exhibited PCO2-dependent, positive straight line relationships to arterial pH. An increment in biliary HCO3- secretion of 17 (11-24)% was seen during high PCO2 at pH 7.40. In group II, biliary HCO3- secretion exhibited PCO2-dependent, positive curvilinear relationships to arterial pH. A median increment in HCO3- secretion of 37 (20-62)% was seen during elevated PCO2 at arterial pH 7.40. The linear dependence of ductular HCO3- secretion on arterial pH and the effect of elevated PCO2 on HCO3- secretion fit well with findings in other epithelia, where proton transport is thought be driven by a proton pump. A computer simulation provided evidence suggesting that secretin-dependent HCO3- secretion does not involve the action of a Na+/H+ ion exchanger--in contrast to UDCA-dependent HCO3- secretion. It is concluded that ductular and canalicular HCO3- secretion could be mediated by a proton pump and a Na+/H+ ion exchanger in addition to canalicular HCO3- secretion due to solvent drag and diffusion, respectively.

Animals↗
PubMed1987

DCCD (N,N'-dicyclohexylcarbodiimide) inhibits biliary secretion of HCO-3.

To study whether a proton pump is an integral part of the mechanism responsible for secretin-dependent biliary secretion of HCO-3 ions, the proton pump inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) was systemically administered to six anesthetized, secretin-infused pigs. Because biliary HCO-3 secretion varies with arterial pH, secretion rate was measured at several different arterial pH values, before and after DCCD (25 mumol/kg). At arterial pH 7.45, bile flow was 2.1 (1.6-2.9) ml/min, and HCO-3 secretion was 224 (157-311) mumol/min. DCCD reduced bile flow and HCO-3 secretion by 30% and 40%, respectively, independent of arterial pH. In contrast, bile acid secretion, 46 (41-59) mumol/min, was not changed by DCCD. The hepatic adenosine triphosphatase (ATP) level, 2.0 (1.8-2.1) mumol/g wet tissue, was not changed by DCCD. DCCD (10(-4) mol/l) affected neither Na,K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. The reduction in biliary HCO-3 secretion induced by the proton pump inhibitor DCCD may indicate that a proton pump is integrated into the mechanism responsible for secretin-dependent biliary secretion of HCO-3.

Adenosine Triphosphate↗
PubMed1986

Lack of effect of amiloride, furosemide, bumetanide and triamterene on pancreatic NaHCO3 secretion in pigs.

This study examines the effects of the Na entry blockers amiloride, furosemide, bumetanide and triamterene on pancreatic NaHCO3 secretion. The purpose of the study was to elucidate whether Na flux through a Na-H-antiport, a Na,K,Cl-symport or a Na-K(H)-antiport respectively, may be rate limiting for pancreatic NaHCO3 secretion. The effect of each drug on secretion was tested in four groups of six anaesthetized pigs (20-25 kg body wt) during supramaximal, intravenous secretin infusion (3.0 CU kg-1 body wt. h-1), following laparotomy and cannulation of the pancreatic duct. Secretion was measured over a wide range of arterial pH values, both before and after drug administration in each animal. Pancreatic NaHCO3 secretion averaged 268 (219-308) mumol min-1 at physiological arterial pH 7.40 in the control period. Neither amiloride (90 mg kg-1 body wt), furosemide (10 mg kg-1 body wt), bumetanide (0.6 mg kg-1 body wt) nor triamterene (25 mg kg-1 body wt) affected the rate of secretin-dependent NaHCO3 secretion or the relation between NaHCO3 secretion and arterial pH. It is concluded that Na flux through neither a Na-H-antiport, a Na,K,Cl-symport nor a Na-K(H)-antiport appears to be rate limiting for pancreatic secretion of NaHCO3.

Amiloride↗
PubMed1986

Histochemical localization of carbonic anhydrase in the pig's exocrine pancreas.

Carbonic anhydrase is essential for the pancreatic secretion of NaHCO3. To localize the distribution of carbonic anhydrase in the exocrine gland and, hence, identify the potential cellular source of secreted NaHCO3, histochemical staining of carbonic anhydrase was carried out on pancreatic biopsies obtained from six pigs at both supramaximal intravenous secretin stimulation and at secretory rest. Tissue staining, using Hansson's technique, revealed a strong staining both in membranes and cytoplasm in the duct cells and a weaker cytoplasmic staining in the acinar cells. Staining reaction was abolished by 10(-5) mol l-1 acetazolamide. Duct cells, accordingly, seem to be responsible for NaHCO3 secretion, while acinar cells appear unlikely to contribute substantially to NaHCO3 secretion.

Acetazolamide↗
PubMed1986

NN'-dicyclohexylcarbodiimide (DCCD) reduces pancreatic NaHCO3 secretion without changing pancreatic tissue ATP levels.

To study the mechanism responsible for pancreatic NaHCO3 secretion, the inhibitor NN'-dicyclohexylcarbodiimide (DCCD) was administered to six secretin-infused, anaesthetized pigs. Pancreatic juice was collected from a catheter in the main pancreatic duct. Secretion rate was measured at several arterial pH values in each animal, both before and after DCCD. 15 (14-30) mumol kg-1 body wt DCCD, intra-arterially, reduced pancreatic NaHCO3 secretion from 296 (234-398) to 181 (134-237) mumol min-1 at arterial pH 7.43 (7.42-7.47). Similar fractional reductions of secretion occurred at lower arterial pH. Pancreatic tissue ATP concentration, 1.8 (1.4-2.0) mumol g-1 wet wt, was not changed by DCCD. DCCD, less than or equal to 10(-4) mol l-1, did not change Na,K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. It is concluded that DCCD reduced pancreatic NaHCO3 secretion by a mechanism not involving ATP depletion nor inhibition of Na,K-ATPase nor carbonic anhydrase activities in pancreatic cells. Because DCCD inhibits proton pumps, DCCD may have reduced NaHCO3 secretion through interfering with a proton pump involved in extruding H+ from HCO-3 secreting cells to interstitial fluid in the pancreas.

Adenosine Triphosphate↗
PubMed1985

Effects of digitoxin and hypokalaemia on pancreatic NaHCO3 secretion and pancreatic Na,K-ATPase activity.

To study the role played by Na,K-ATPase in the pancreatic secretion of NaHCO3, experiments were performed in 20 anaesthetized, secretin-infused pigs (3.0 clinical units X kg b. wt. X h-I). The relationship between pancreatic NaHCO3 secretion and arterial pH was obtained before and during Na,K-ATPase inhibition by digitoxin and hypokalaemia. Na,K-ATPase activity in pancreatic tissue homogenate averaged 5.45 (5.02-6.68) mumol Pi X mg X protein X h-I. Retrograde injection of 0.5 ml 1.4 X 10(-4) mol X l-I digitoxin into pancreatic ducts reduced pancreatic Na,K-ATPase activity by 3I(I8-47)%, while intra-arterial injection of 0.2 mg X kg b. wt-I digitoxin reduced pancreatic Na,K-ATPase activity by 50(45-56)%. Digitoxin and hypokalaemia reduced the rate of pancreatic NaHCO3 and shifted the normal, proportional relationship between NaHCO3 secretion and arterial pH towards higher pH. Hypokalaemia reduced Na,K-ATPase activity and NaHCO3 secretion in proportion. These effects indicate that Na,K-ATPase helps to sustain the requisite electrochemical potential gradients for driving H+ ions, and hence HCO-3 ions, out of secretory cells.

Animals↗