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. 1980 May;302:107–120. doi: 10.1113/jphysiol.1980.sp013232

The influence of micelle formation on bile salt secretion.

E R O'Máille
PMCID: PMC1282837  PMID: 7411450

Abstract

1. The influence of micelle formation on bile salt secretion was assessed by analysing the secretory characteristics of, and interaction between, the natural micelle-forming bile salts, taurocholate and cholate, and the artificial non-micelle-forming bile salts, taurodehydrocholate and dehydrocholate (both of which are subjected to reductive metabolism), in anaesthetized dogs. 2. Competitive secretory interaction between these two classes of bile salt was demonstrated thereby indicating that they share the same biliary transport system. Taurodehydrocholate had a lower affinity for the transport system than that of taurocholate and the metabolic derivatives of dehydrocholate. 3. The (initially determined) biliary secretory maxima for taurodehydrocholate (4 . 9 +/- 1 . 9 (S.D.) mumole/min. kg, n = 6) and total 'dehydrocholate' in taurine replete dogs (4 . 2 +/- 1 . 0 mumole/min. kg, n = 16) were both significantly less than those for taurocholate (8 . 0 +/- 1 . 8 mumole/min. kg, n = 16) and total cholate in taurine replete dogs (6 . 9 +/- 1 . 2 mumole/min. kg, n = 12). 4. The initially determined secretory maxima of taurodehydrocholate and 'dehydrocholate' were elevated by about 30 and 36%, respectively, by an earlier period of taurocholate administration; the most likely explanation (which is supported by independent morphological studies) for this effect is that taurocholate increases the number of functional 'carriers' in the canalicular membrane. When calculated for optimal conditions, the secretory maxima of the non-micelle-forming bile salts closely approached those of the micelle formers. 5. The above results would seem to indicate that micelle formation (in the hepatocyte, canalicular membrane or bile) is not essential for the effective translocation of bile salt by the specific canalicular membrane receptors. The results also suggest that the effective concentration of bile salt in bile (possibly 60--70 times greater in the case of the non-micelle-formers) is not an important determinant of the net secretory performance of conjugated bile salt. 6. At the same bile salt secretion rate (3 . 06 mumole/min. kg), the bile flow rate associated with taurodehydrocholate (44 . 3 +/- 2 . 7 (S.D. along regression line) microliter/min. kg, n = 38) was significantly greater than that associated with taurocholate (29 . 5 +/- 7 . 7 microliter/min. kg, n = 80) but significantly less than that associated with 'dehydrocholate' in taurine replete dogs (51 . 7 +/- 4 . 8 microliter./min. kg, n = 33), 'dehydrocholate' after acute taurine depletion (61 . 2 microliter./min. kg, n = 1) and free cholate after taurine depletion (49 . 8 +/- 9 . 8 microliter/min. kg, n = 92). The extra flow associated with the free bile salts is derived by means that are largely or entirely independent of their osmotic activity in bile.

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Selected References

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  1. Accatino L., Simon F. R. Identification and characterization of a bile acid receptor in isolated liver surface membranes. J Clin Invest. 1976 Feb;57(2):496–508. doi: 10.1172/JCI108302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adler R. D., Wannagat F. J., Ockner R. K. Bile secretion in selective biliary obstruction. Adaptation of taurocholate transport maximum to increased secretory load in the rat. Gastroenterology. 1977 Jul;73(1):129–136. [PubMed] [Google Scholar]
  3. Carey M. C., Small D. M. Micelle formation by bile salts. Physical-chemical and thermodynamic considerations. Arch Intern Med. 1972 Oct;130(4):506–527. [PubMed] [Google Scholar]
  4. Cowen A. E., Korman M. G., Hofmann A. F., Thomas P. J. Plasma disappearance of radioactivity after intravenous injection of labeled bile acids in man. Gastroenterology. 1975 Jun;68(6):1567–1573. [PubMed] [Google Scholar]
  5. Diamond J. M., Wright E. M. Biological membranes: the physical basis of ion and nonelectrolyte selectivity. Annu Rev Physiol. 1969;31:581–646. doi: 10.1146/annurev.ph.31.030169.003053. [DOI] [PubMed] [Google Scholar]
  6. Duane W. C. Taurocholate- and taurochenodeoxycholate-lecithin micelles: the equilibrium of bile salt between aqueous phase and micelle. Biochem Biophys Res Commun. 1977 Jan 10;74(1):223–229. doi: 10.1016/0006-291x(77)91397-3. [DOI] [PubMed] [Google Scholar]
  7. Forker E. L. Mechanisms of hepatic bile formation. Annu Rev Physiol. 1977;39:323–347. doi: 10.1146/annurev.ph.39.030177.001543. [DOI] [PubMed] [Google Scholar]
  8. HOFMANN A. F. CLINICAL IMPLICATIONS OF PHYSICOCHEMICAL STUDIES ON BILE SALTS. Gastroenterology. 1965 Apr;48:484–494. [PubMed] [Google Scholar]
  9. Heaton K. W., Lack L. Ileal bile salt transport: mutual inhibition in an in vivo system. Am J Physiol. 1968 Mar;214(3):585–590. doi: 10.1152/ajplegacy.1968.214.3.585. [DOI] [PubMed] [Google Scholar]
  10. Hofmann A. F., Small D. M. Detergent properties of bile salts: correlation with physiological function. Annu Rev Med. 1967;18:333–376. doi: 10.1146/annurev.me.18.020167.002001. [DOI] [PubMed] [Google Scholar]
  11. Layden T. J., Boyer J. L. Influence of bile acids on bile canalicular membrane morphology and the lobular gradient in canalicular size. Lab Invest. 1978 Aug;39(2):110–119. [PubMed] [Google Scholar]
  12. Nemchausky B. A., Layden T. J., Boyer J. L. Effects of chronic choleretic infusions of bile acids on the membrane of the bile canaliculus. A biochemical and morphologic study. Lab Invest. 1977 Mar;36(3):259–267. [PubMed] [Google Scholar]
  13. O'Máille E. R. Bile salt secretion. Ir J Med Sci. 1977 Jul;146(7):190–198. doi: 10.1007/BF03030959. [DOI] [PubMed] [Google Scholar]
  14. O'Máille E. R., Richards T. G. Possible explanations for the differences in secretory characteristics between conjugated and free bile acids. J Physiol. 1977 Mar;265(3):855–866. doi: 10.1113/jphysiol.1977.sp011748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. O'Máille E. R., Richards T. G., Short A. H. Acute taurine depletion and maximal rates of hepatic conjugation and secretion of cholic acid in the dog. J Physiol. 1965 Sep;180(1):67–79. [PMC free article] [PubMed] [Google Scholar]
  16. O'Máille E. R., Richards T. G., Short A. H. Factors determining the maximal rate of organic anion secretion by the liver and further evidence on the hepatic site of action of the hormone secretin. J Physiol. 1966 Oct;186(2):424–438. doi: 10.1113/jphysiol.1966.sp008044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Máille E. R., Richards T. G., Short A. H. Observations on the elimination rates of single injections of taurocholate and cholate in the dog. Q J Exp Physiol Cogn Med Sci. 1969 Jul;54(3):296–310. doi: 10.1113/expphysiol.1969.sp002028. [DOI] [PubMed] [Google Scholar]
  18. O'Máille E. R., Richards T. G., Short A. H. The influence of conjugation of cholic acid on its uptake and secretion: hepatic extraction of taurocholate and cholate in the dog. J Physiol. 1967 Apr;189(2):337–350. doi: 10.1113/jphysiol.1967.sp008172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. O'Máille E. R., Richards T. G. The secretory characteristics of dehydrocholate in the dog: comparison with the natural bile salts. J Physiol. 1976 Oct;261(2):337–357. doi: 10.1113/jphysiol.1976.sp011562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. PREISIG R., COOPER H. L., WHEELER H. O. The relationship between taurocholate secretion rate and bile production in the unanesthetized dog during cholinergic blockade and during secretin administration. J Clin Invest. 1962 May;41:1152–1162. doi: 10.1172/JCI104568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rutishauser S. C., Stone S. L. Comparative effects of sodium taurodeoxycholate and sodium taurocholate on bile secretion in the rat, dog and rabbit. J Physiol. 1975 Mar;245(3):583–598. doi: 10.1113/jphysiol.1975.sp010863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Scharschmidt B. F., Schmid R. The micellar sink: a quantitative assessment of the association of organic anions with mixed micelles and other macromolecular aggregates in rat bile. J Clin Invest. 1978 Dec;62(6):1122–1131. doi: 10.1172/JCI109231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Soloway R. D., Hofmann A. F., Thomas P. J., Schoenfield L. J., Klein P. D. Triketocholanoic (dehydrocholic) acid. Hepatic metabolism and effect on bile flow and biliary lipid secretion in man. J Clin Invest. 1973 Mar;52(3):715–724. doi: 10.1172/JCI107233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wannagat R. J., Adler R. D., Ockner R. K. Bile acid-induced increase in bile acid-independent flow and plasma membrane NaK-ATPase activity in rat liver. J Clin Invest. 1978 Feb;61(2):297–307. doi: 10.1172/JCI108939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wheeler H. O., King K. K. Biliary excretion of lecithin and cholesterol in the dog. J Clin Invest. 1972 Jun;51(6):1337–1350. doi: 10.1172/JCI106930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wheeler H. O., Ross E. D., Bradley S. E. Canalicular bile production in dogs. Am J Physiol. 1968 Apr;214(4):866–874. doi: 10.1152/ajplegacy.1968.214.4.866. [DOI] [PubMed] [Google Scholar]
  27. Wheeler H. O. Secretion of bile acids by the liver and their role in the formation of hepatic bile. Arch Intern Med. 1972 Oct;130(4):533–541. [PubMed] [Google Scholar]
  28. Young D. L., Hanson K. C. Effect of bile salts on hepatic phosphatidylcholine synthesis and transport into rat bile. J Lipid Res. 1972 Mar;13(2):244–252. [PubMed] [Google Scholar]

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