Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Sep;89(1):199–205. doi: 10.1111/j.1476-5381.1986.tb11136.x

Impairment of protein synthesis in the rat uterus following intrauterine delivery of indomethacin.

P R Hurst, P V Peplow
PMCID: PMC1917047  PMID: 2432978

Abstract

When indomethacin was incorporated into a slow-release preparation (initial content 1.6 mg drug) and placed in one horn of the rat uterus, a significant decrease in protein synthesis occurred for this horn in comparison with control animals (as determined by the incorporation of radioactive leucine) at three different times after insertion. Decreases of 20, 21% at the two times of dioestrus and 28% at the time of oestrus selected were determined. No significant reduction in protein synthesis was found for the contralateral horn, although there was a tendency for it to be lowered at the earliest time of examination when two complete oestrous cycles had passed following insertion. Measurement of the uptake of radioactive leucine by the uterine horns showed no change in response to indomethacin delivery compared to the control animals with silastic implants, and suggested that the transport system for this amino acid in cells of the uterine horns was not affected by the drug. It was apparent that in instances when the protein synthesis of the uterine horn was impaired by indomethacin that a decrease in RNA/DNA ratio existed. At the latest time examined, no alteration in DNA content occurred in the indomethacin-influenced horn but there was a significant reduction in RNA content. For a small proportion of the animals with indomethacin-releasing preparations there was a tendency to show a lengthening of the oestrous cycle over the first three cycles following insertion. Whether this was due to a direct effect of indomethacin on the ovaries or an effect caused by decreased concentrations of prostaglandins in the uterus was unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
205

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bayer B. M., Kruth H. S., Vaughan M., Beaven M. A. Arrest of cultured cells in the G1 phase of the cell cycle by indomethacin. J Pharmacol Exp Ther. 1979 Jul;210(1):106–111. [PubMed] [Google Scholar]
  3. Bayer B. M., Lo T. N., Beaven M. A. Anti-inflammatory drugs alter amino acid transport in HTC cells. J Biol Chem. 1980 Sep 25;255(18):8784–8790. [PubMed] [Google Scholar]
  4. Blatchley F. R., Donovan B. T. Luteolytic effect of prostaglandin in the guinea-pig. Nature. 1969 Mar 15;221(5185):1065–1066. doi: 10.1038/2211065a0. [DOI] [PubMed] [Google Scholar]
  5. Burleigh M., Smith M. J. The site of the inhibitory action of salicylate on protein biosynthesis in vitro. Biochem J. 1970 Apr;117(3):68P–68P. doi: 10.1042/bj1170068pa. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cashin C. H., Dawson W., Kitchen E. A. The pharmacology of benoxaprofen (2-[4-chlorophenyl]-alpha-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with antiinflammatory activity apparently unrelated to inhibition of prostaglandin synthesis. J Pharm Pharmacol. 1977 Jun;29(6):330–336. doi: 10.1111/j.2042-7158.1977.tb11330.x. [DOI] [PubMed] [Google Scholar]
  7. Christensen H. N. Amino acid transport systems in animal cells: interrelations and energization. J Supramol Struct. 1977;6(2):205–213. doi: 10.1002/jss.400060206. [DOI] [PubMed] [Google Scholar]
  8. Dawkins P. D., Gould B. J., Smith M. J. Inhibitory effect of salicylate on the incorporation of L-(U-14C)leucine into the protein of rat tissue preparations in vitro. Biochem J. 1966 Jun;99(3):703–707. doi: 10.1042/bj0990703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
  10. Horton E. W., Poyser N. L. Elongation of oestrous cycle in the guinea-pig following subcutaneous or intra-uterine administration of indomethacin. Br J Pharmacol. 1973 Sep;49(1):98–105. [PubMed] [Google Scholar]
  11. Hurst P. R., Peplow P. V. Suppression of leukocytosis by the intrauterine delivery of high doses of indomethacin in the rat. Contraception. 1985 May;31(5):445–452. doi: 10.1016/0010-7824(85)90080-0. [DOI] [PubMed] [Google Scholar]
  12. Janakidevi K., Smith M. J. Effects of salicylate on RNA polymerase activity and on the incorporation of orotic acid and thymidine into the nucleic acids of rat foetuses in vitro. J Pharm Pharmacol. 1970 Apr;22(4):249–252. doi: 10.1111/j.2042-7158.1970.tb08514.x. [DOI] [PubMed] [Google Scholar]
  13. Janakidevi K., Smith M. J. Effects of salicylate on the incorporation of orotic acid into nucleic acids of mouse tissues in vivo. J Pharm Pharmacol. 1970 Jan;22(1):51–55. doi: 10.1111/j.2042-7158.1970.tb08384.x. [DOI] [PubMed] [Google Scholar]
  14. Janakidevi K., Smith M. J. Inhibition of nucleic acid polymerases by salicylate in vitro. J Pharm Pharmacol. 1969 Jun;21(6):401–402. doi: 10.1111/j.2042-7158.1969.tb08278.x. [DOI] [PubMed] [Google Scholar]
  15. Kalbhen D. A., Karzel K., Domenjoz R. The inhibitory effects of some antiphlogistic drugs on the glucosamine incorporation into mucopolysaccharides synthesized by fibroblast cultures. Med Pharmacol Exp Int J Exp Med. 1967;16(3):185–189. doi: 10.1159/000136987. [DOI] [PubMed] [Google Scholar]
  16. Kilberg M. S., Handlogten M. E., Christensen H. N. Characteristics of an amino acid transport system in rat liver for glutamine, asparagine, histidine, and closely related analogs. J Biol Chem. 1980 May 10;255(9):4011–4019. [PubMed] [Google Scholar]
  17. Kuehl F. A., Jr, Egan R. W. Prostaglandins, arachidonic acid, and inflammation. Science. 1980 Nov 28;210(4473):978–984. doi: 10.1126/science.6254151. [DOI] [PubMed] [Google Scholar]
  18. Marcus G. J. Mitosis in the rat uterus during the estrous cycle, early pregnancy, and early pseudopregnancy. Biol Reprod. 1974 May;10(4):447–452. doi: 10.1095/biolreprod10.4.447. [DOI] [PubMed] [Google Scholar]
  19. Miller B. G. Delayed interactions between progesterone and low doses of 17 beta-estradiol in the mouse uterus. Endocrinology. 1979 Jan;104(1):26–33. doi: 10.1210/endo-104-1-26. [DOI] [PubMed] [Google Scholar]
  20. Peplow P. V., Hurst P. R. An intrauterine silastic system for the sustained release of indomethacin. Prostaglandins Med. 1981 Dec;7(6):563–569. doi: 10.1016/0161-4630(81)90046-x. [DOI] [PubMed] [Google Scholar]
  21. Rainsford K. D. The effects of aspirin and other non-steroid anti-inflammatory/analgesic drugs on gastro-intestinal mucus glycoprotein biosynthesis in vivo: relationship to ulcerogenic actions. Biochem Pharmacol. 1978 Mar 15;27(6):877–885. doi: 10.1016/0006-2952(78)90412-4. [DOI] [PubMed] [Google Scholar]
  22. Reid R. J., Heald P. J. Protein metabolism of the rat uterus during the oestrous cycle, pregnancy and pseudopregnancy, and as affected by an anti-implantation compounds, ICI 46,474. J Reprod Fertil. 1971 Oct;27(1):73–82. doi: 10.1530/jrf.0.0270073. [DOI] [PubMed] [Google Scholar]
  23. Reunanen M., Hänninen O., Hartiala K. Inhibitory effect of salicylates and cinchophen derivatives on amino-acid incorporation. Nature. 1967 Mar 4;213(5079):918–919. doi: 10.1038/213918a0. [DOI] [PubMed] [Google Scholar]
  24. Smith M. J. Prostaglandins and aspirin: an alternative view. Agents Actions. 1975 Oct;5(4):315–317. doi: 10.1007/BF02205237. [DOI] [PubMed] [Google Scholar]
  25. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES