Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1975 Jul;54(3):309–317. doi: 10.1111/j.1476-5381.1975.tb07570.x

Potency and selectivity of methyl analogues of prostaglandin E2 on rat gastrointestinal function.

I H Main, B J Whittle
PMCID: PMC1666480  PMID: 1164591

Abstract

1 The potency and selectivity of action of prostaglandin E2 and its (15S)- or (15R)-15 methyl and 16, 16 dimethyl analogues on gastrointestinal function have been studied in the rat. 2 The (15S)-15 methyl and 16, 16 dimethyl analogues were 40 times as active as prostaglandin E2 in inhibiting pentagastrin-stimulated acid secretion on intravenous administration to the anaesthetized rat, and 100 times as active on subcutaneous injection to the chronic fistula rat. 3 In antisecretory doses, the analogues, like prostaglandin E2, caused bile reflux and, in higher doses, profuse diarrhoea. 4 The (15S)-15 methyl and 16, 16 dimethyl analogues were at least 30 times as active as prostaglandin E2 in causing changes in intestinal intraluminal pressure in vivo, but were equipotent on isolated smooth muscle. 5 In equivalent antisecretory doses, the methyl analogues had little effect on systemic arterial blood pressure and resting mucosal blood flow compared with prostaglandin E2. 6 The (15R) methyl epimer administered parenterally had little effect on gastrointestinal function but brief acid incubation greatly increased its activity.

Full text

PDF
309

Selected References

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

  1. Ballard C. A., Qilligan E. J. Midtrimester abortion with intramuscular injection of 15-methyl-prostaglandin E2. Contraception. 1974 May;9(5):523–529. doi: 10.1016/0010-7824(74)90063-8. [DOI] [PubMed] [Google Scholar]
  2. Bertaccini G., Impicciatore M., De Caro G. Action of caerulein and related substances on the pyloric sphincter of the anaesthetized rat. Eur J Pharmacol. 1973 Jun;22(3):320–324. doi: 10.1016/0014-2999(73)90032-0. [DOI] [PubMed] [Google Scholar]
  3. Borella L. E., Herr F. A new method for measuring gastric acid secretion in unanesthetized rats. Gastroenterology. 1971 Sep;61(3):345–356. [PubMed] [Google Scholar]
  4. Classen M., Koch H., Bickhardt J., Topf G., Demling L. The effect of prostaglandin E 1 on the pentagastrin-stimulated gastric secretion in man. Digestion. 1971;4(6):333–344. doi: 10.1159/000197138. [DOI] [PubMed] [Google Scholar]
  5. Horton E. W., Main I. H., Thompson C. J., Wright P. M. Effect of orally administered prostaglandin E1 on gastric secretion and gastrointestinal motility in man. Gut. 1968 Dec;9(6):655–658. doi: 10.1136/gut.9.6.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Karim S. M., Carter D. C., Bhana D., Ganesan P. A. Effect of orally administered prostaglandin E 2 and its 15-methyl analogues on gastric secretion. Br Med J. 1973 Jan 20;1(5846):143–146. doi: 10.1136/bmj.1.5846.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Karim S. M., Sivasamboo R., Ratnam S. S. Abortifacient action of orally administered 16,16 dimethyl prostaglandin E2 and its methyl ester. Prostaglandins. 1974 May 25;6(4):349–354. doi: 10.1016/s0090-6980(74)80009-2. [DOI] [PubMed] [Google Scholar]
  8. Main I. H., Whittle B. J. Gastric mucosal blood flow during pentagastrin- and histamine-stimulated acid secretion in the rat. Br J Pharmacol. 1973 Nov;49(3):534–542. doi: 10.1111/j.1476-5381.1973.tb17264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Main I. H., Whittle B. J. Proceedings: Failure of burimamide and (15S)-15-methyl prostaglandin E2 to prevent histamine-induced gastric mucosal hyperaemia in the rat. J Physiol. 1974 Jun;239(2):118P–119P. [PubMed] [Google Scholar]
  10. Main I. H., Whittle B. J. Prostaglandin E2 and the stimulation of rat gastric acid secretion by dibutyryl cyclic 3',5'-AMP. Eur J Pharmacol. 1974 May;26(2):204–211. doi: 10.1016/0014-2999(74)90229-5. [DOI] [PubMed] [Google Scholar]
  11. Main I. H., Whittle B. J. The effects E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat. Br J Pharmacol. 1973 Nov;49(3):428–436. doi: 10.1111/j.1476-5381.1973.tb17253.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Robert A., Mylander B., Andersson S. Marked inhibition of gastric secretion by two prostaglandin analogs given orally to man. Life Sci. 1974 Feb 1;14(3):533–538. doi: 10.1016/0024-3205(74)90367-1. [DOI] [PubMed] [Google Scholar]
  13. Robert A., Nezamis J. E., Phillips J. P. Effect of prostaglandin E1 on gastric secretion and ulcer formation in the rat. Gastroenterology. 1968 Oct;55(4):481–487. [PubMed] [Google Scholar]
  14. Strand J. C., Miller M. P., McGiff J. C. Biological activity of the methyl esters of prostaglandin E2 and its (15S)-15-methyl analogue. Eur J Pharmacol. 1974 May;26(2):151–157. doi: 10.1016/0014-2999(74)90221-0. [DOI] [PubMed] [Google Scholar]
  15. Weeks J. R., DuCharme D. W., Magee W. E., Miller W. L. The biological activity of the (15S)-15-methyl analogs of prostaglandins. E2 and F2a. J Pharmacol Exp Ther. 1973 Jul;186(1):67–74. [PubMed] [Google Scholar]

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

RESOURCES