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. 1983 Jan 15;210(1):157–166. doi: 10.1042/bj2100157

Effect of halothane on metabolism of 5-hydroxytryptamine by rat lungs perfused in situ.

C A Watkins, S A Wartell, D E Rannels
PMCID: PMC1154201  PMID: 6847641

Abstract

The effect of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on the uptake of 14C-labelled 5-hydroxytryptamine (5-HT) and its metabolism to 5-hydroxyindol-3-ylacetic acid (5-HIAA) was investigated in rat lungs perfused in situ. The rate of accumulation of 14C-labelled 5-HIAA in the tissue, monitored as an index of 5-HT metabolism, was linear with time, displayed saturation kinetics and remained stable for at least 180 min of perfusion. Exposure of the lungs to halothane (4%) for 60 min reversibly reduced production of 5-HIAA through an increase in the apparent Km for metabolism of the amine from 1.45 to 3.52 microM (P less than 0.001); the anaesthetic had no effect on the Vmax. of the process. The magnitude of the inhibition increased with time of exposure to the anaesthetic. Halothane exposure did not alter the distribution of [3H]sorbitol or [14C]5-HT, pulmonary vascular resistance, levels of ATP or the kinetics of amino acid transport in the tissue. Inhibition of protein synthesis by cycloheximide did not mimic the effect of the anaesthetic. These observations, together with those made in lungs exposed to inhibitors of 5-HT uptake and metabolism, were consistent with a halothane-mediated inhibition of 5-HT uptake, which did not appear to involve non-specific changes in membrane permeability.

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Selected References

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  1. Bakhle Y. S., Block A. J. Effects of halothane on pulmonary inactivation of noradrenaline and prostaglandin E2 in anaesthetized dogs. Clin Sci Mol Med. 1976 Jan;50(1):87–90. doi: 10.1042/cs0500087. [DOI] [PubMed] [Google Scholar]
  2. Block E. R., Fisher A. B. Depression of serotonin clearance by rat lungs during oxygen exposure. J Appl Physiol Respir Environ Exerc Physiol. 1977 Jan;42(1):33–38. doi: 10.1152/jappl.1977.42.1.33. [DOI] [PubMed] [Google Scholar]
  3. Block E. R., Fisher A. B. Effect of hyperbaric oxygen exposure on pulmonary clearance of 5-hydroxytryptamine. J Appl Physiol Respir Environ Exerc Physiol. 1977 Aug;43(2):254–257. doi: 10.1152/jappl.1977.43.2.254. [DOI] [PubMed] [Google Scholar]
  4. Block E. R., Fisher A. B. Hyperoxia and lung serotonin clearance: a new observation. Chest. 1977 Feb;71(2 Suppl):289–291. doi: 10.1378/chest.71.2.289. [DOI] [PubMed] [Google Scholar]
  5. Block E. R., Stalcup S. A. Depression of serotonin uptake by cultured endothelial cells exposed to high O2 tension. J Appl Physiol Respir Environ Exerc Physiol. 1981 Jun;50(6):1212–1219. doi: 10.1152/jappl.1981.50.6.1212. [DOI] [PubMed] [Google Scholar]
  6. Crapo J. D., Barry B. E., Foscue H. A., Shelburne J. Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen. Am Rev Respir Dis. 1980 Jul;122(1):123–143. doi: 10.1164/arrd.1980.122.1.123. [DOI] [PubMed] [Google Scholar]
  7. Eyring H., Woodbury J. W., D'Arrigo J. S. A molecular mechanism of general anesthesia. Anesthesiology. 1973 May;38(5):415–424. doi: 10.1097/00000542-197305000-00001. [DOI] [PubMed] [Google Scholar]
  8. Gillis C. N., Cronau L. H., Mandel S., Hammond G. L. Indicator dilution measurement of 5-hydroxytryptamine clearance by human lung. J Appl Physiol Respir Environ Exerc Physiol. 1979 Jun;46(6):1178–1183. doi: 10.1152/jappl.1979.46.6.1178. [DOI] [PubMed] [Google Scholar]
  9. Gillis C. N., Roth J. A. Pulmonary disposition of circulating vasoactive hormones. Biochem Pharmacol. 1976 Dec 1;25(23):2547–2553. doi: 10.1016/0006-2952(76)90508-6. [DOI] [PubMed] [Google Scholar]
  10. Haies D. M., Gil J., Weibel E. R. Morphometric study of rat lung cells. I. Numerical and dimensional characteristics of parenchymal cell population. Am Rev Respir Dis. 1981 May;123(5):533–541. doi: 10.1164/arrd.1981.123.5.533. [DOI] [PubMed] [Google Scholar]
  11. Halevy S., Spector S., Altura B. M. Serum serotonin levels determined by radioimmunoassay in normal male and female rats and after intestinal ischemia shock. Biochem Med. 1980 Apr;23(2):236–238. doi: 10.1016/0006-2944(80)90077-0. [DOI] [PubMed] [Google Scholar]
  12. Hammer J. A., 3rd, Rannels D. E. Effects of halothane on protein synthesis and degradation in rabbit pulmonary macrophages. Am Rev Respir Dis. 1981 Jul;124(1):50–55. doi: 10.1164/arrd.1981.124.1.50. [DOI] [PubMed] [Google Scholar]
  13. Hughes J., Gillis C. N., Bloom F. E. The uptake and disposition of dl-norepinephrine in perfused rat lung. J Pharmacol Exp Ther. 1969 Oct;169(2):237–248. [PubMed] [Google Scholar]
  14. Iwasawa Y., Gillis C. N., Aghajanian G. Hypothermic inhibition of 5-hydroxytryptamine and norepinephrine uptake by lung: cellular location of amines after uptake. J Pharmacol Exp Ther. 1973 Sep;186(3):498–507. [PubMed] [Google Scholar]
  15. Jonsson J., Lewander T. A method for the simultaneous determination of 5-hydroxy-3-indole-acetic acid (5-HIAA) and 5-hydroxytryptamine (5-HT) in brain tissue and cerebrospinal fluid. Acta Physiol Scand. 1970 Jan;78(1):43–51. doi: 10.1111/j.1748-1716.1970.tb04637.x. [DOI] [PubMed] [Google Scholar]
  16. Junod A. F. Metabolism of vasoactive agents in lung. Am Rev Respir Dis. 1977 Jun;115(6 Pt 2):51–57. doi: 10.1164/arrd.1977.115.S.51. [DOI] [PubMed] [Google Scholar]
  17. Junod A. F. Uptake, metabolism and efflux of 14 C-5-hydroxytryptamine in isolated perfused rat lungs. J Pharmacol Exp Ther. 1972 Nov;183(2):341–355. [PubMed] [Google Scholar]
  18. Leuenberger P. J., Stalcup S. A., Mellins R. B., Greenbaum L. M., Turino G. M. Decrease in angiotensin I conversion by acute hypoxia in dogs. Proc Soc Exp Biol Med. 1978 Sep;158(4):586–589. doi: 10.3181/00379727-158-40252. [DOI] [PubMed] [Google Scholar]
  19. Mason R. J., Williams M. C., Greenleaf R. D., Clements J. A. Isolation and properties of type II alveolar cells from rat lung. Am Rev Respir Dis. 1977 Jun;115(6):1015–1026. doi: 10.1164/arrd.1977.115.6.1015. [DOI] [PubMed] [Google Scholar]
  20. Naito H., Gillis C. N. Effects of halothane and nitrous oxide on removal of norepinephrine from the pulmonary circulation. Anesthesiology. 1973 Dec;39(6):575–580. doi: 10.1097/00000542-197312000-00003. [DOI] [PubMed] [Google Scholar]
  21. Ng K. K., Vane J. R. Fate of angiotensin I in the circulation. Nature. 1968 Apr 13;218(5137):144–150. doi: 10.1038/218144a0. [DOI] [PubMed] [Google Scholar]
  22. Nicholas T. E., Strum J. M., Angelo L. S., Junod A. F. Site and mechanism of uptake of 3H--norepinephrine by isolated perfused rat lungs. Circ Res. 1974 Nov;35(5):670–680. doi: 10.1161/01.res.35.5.670. [DOI] [PubMed] [Google Scholar]
  23. Pennock J. L., Pierce W. S., Waldhausen J. A. The management of the lungs during cardiopulmonary bypass. Surg Gynecol Obstet. 1977 Dec;145(6):917–927. [PubMed] [Google Scholar]
  24. Pickett R. D., Anderson M. W., Orton T. C., Eling T. E. The pharmacodynamics of 5-hydroxytryptamine uptake and metabolism by the isolated perfused rabbit lung. J Pharmacol Exp Ther. 1975 Sep;194(3):545–553. [PubMed] [Google Scholar]
  25. ROSENBERG J. C. CIRCULATING SEROTONIN AND CATECHOLAMINES FOLLOWING OCCLUSION OF THE SUPERIOR MESENTERIC ARTERY. Ann Surg. 1964 Dec;160:1062–1065. doi: 10.1097/00000658-196412000-00020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rannels D. E., Sahms R. H., Watkins C. A. Effects of starvation and diabetes on protein synthesis in lung. Am J Physiol. 1979 Apr;236(4):E421–E428. doi: 10.1152/ajpendo.1979.236.4.E421. [DOI] [PubMed] [Google Scholar]
  27. Roth J. A., Gillis C. N. Multiple forms of amine oxidase in perfused rabbit lung. J Pharmacol Exp Ther. 1975 Sep;194(3):537–544. [PubMed] [Google Scholar]
  28. Roth R. A., Wiersma D. A. Role of the lung in total body clearance of circulating drugs. Clin Pharmacokinet. 1979 Sep-Oct;4(5):355–367. doi: 10.2165/00003088-197904050-00002. [DOI] [PubMed] [Google Scholar]
  29. Rudnick G. Active transport of 5-hydroxytryptamine by plasma membrane vesicles isolated from human blood platelets. J Biol Chem. 1977 Apr 10;252(7):2170–2174. [PubMed] [Google Scholar]
  30. Seiler K. U., Wassermann O., Wensky H. On the role of serotonin in the pathogenesis of pulmonary hypertension induced by anorectic drugs; an experimental study in the isolated perfused rat lung, II. Fenfluramine, mazindol, mefenorex, phentermine and R 800. Clin Exp Pharmacol Physiol. 1976 Jul-Aug;3(4):323–330. doi: 10.1111/j.1440-1681.1976.tb00608.x. [DOI] [PubMed] [Google Scholar]
  31. Stalcup S. A., Lipset J. S., Legant P. M., Leuenberger P. J., Mellins R. B. Inhibition of converting enzyme activity by acute hypoxia in dogs. J Appl Physiol Respir Environ Exerc Physiol. 1979 Feb;46(2):227–234. doi: 10.1152/jappl.1979.46.2.227. [DOI] [PubMed] [Google Scholar]
  32. Stalcup S. A., Lipset J. S., Woan J. M., Leuenberger P., Mellins R. B. Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia. J Clin Invest. 1979 May;63(5):966–976. doi: 10.1172/JCI109397. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  33. Wartell S. A., Christopherson R., Watkins C. A., Rannels D. E. Inhibition of synthesis of lung proteins by halothane. Mol Pharmacol. 1981 May;19(3):520–524. [PubMed] [Google Scholar]
  34. Watkins C. A., Rannels D. E. In situ perfusion of rat lungs: stability and effects of oxygen tension. J Appl Physiol Respir Environ Exerc Physiol. 1979 Aug;47(2):325–329. doi: 10.1152/jappl.1979.47.2.325. [DOI] [PubMed] [Google Scholar]
  35. Watkins C. A., Rannels D. E. Measurement of protein synthesis in rat lungs perfused in situ. Biochem J. 1980 Apr 15;188(1):269–278. doi: 10.1042/bj1880269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wiersma D. A., Roth R. A. Clearance of 5-hydroxytryptamine by rat lung and liver: the importance of relative perfusion and intrinsic clearance. J Pharmacol Exp Ther. 1980 Jan;212(1):97–102. [PubMed] [Google Scholar]

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