Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1985 Jun;85(2):499–512. doi: 10.1111/j.1476-5381.1985.tb08887.x

Histamine-induced inositol phospholipid breakdown in the longitudinal smooth muscle of guinea-pig ileum.

J Donaldson, S J Hill
PMCID: PMC1916608  PMID: 2992666

Abstract

The characteristics of histamine-stimulated inositol phospholipid breakdown in slices of guinea-pig ileal smooth muscle and cerebellum have been investigated. In cerebellar slices the inhibition of the inositol phospholipid response to histamine by mepyramine was consistent with competitive antagonism of histamine H1-receptors. In slices of the longitudinal smooth muscle of guinea-pig ileum, mepyramine produced only a weak inhibition of the response to histamine, at concentrations up to 1 microM. This was in striking contrast to the potent competitive antagonism of the H1-mediated contractile responses obtained with mepyramine in this tissue. The H1-receptor antagonists (+)-chlorpheniramine and promethazine similarly had no effect on the EC50 value for histamine in guinea-pig ileum, while promethazine competitively antagonized the muscarinic receptor-mediated inositol phospholipid response in this tissue (Ka 3.6 X 10(7)M-1). Cimetidine, on its own, did not significantly inhibit the inositol phosphate accumulation elicited by histamine in ileum. In the presence of 0.2 microM mepyramine, cimetidine (0.1 mM) produced a small parallel shift of the histamine concentration-response curve (Ka 3 X 10(4) M-1). This inhibition, however, was not consistent with antagonism of an H2-receptor-mediated response. The effect of a range of histamine analogues on inositol phospholipid breakdown was determined. Dose-response curves were constructed and characterized in terms of the EC50, slope and maximal response attainable relative to histamine. The H1-agonists, N alpha,N alpha-dimethylhistamine, N alpha-methylhistamine, 2-pyridylethylamine and 2-thiazolyethylamine produced the largest accumulations of [3H]-inositol-1-phosphate. A very weak response was produced by the H2-selective agonist impromidine, while dimaprit (also H2-selective) was without significant effect. Mepyramine appeared to antagonize competitively the response to the H1-selective agonist 2-pyridylethylamine. This was in contrast to the data obtained with other H1-agonists, where mepyramine produced only a small dextral shift of the agonist curves at low agonist concentrations and an increase in the Hill coefficient. This was particularly striking in the case of 2-methylhistamine. The results suggest that an H1-receptor component in guinea-pig ileum, may coexist with a larger inositol phospholipid response to histamine which is independent of the activation of H1- or H2-receptors.

Full text

PDF
509

Selected References

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

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arrang J. M., Garbarg M., Schwartz J. C. Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature. 1983 Apr 28;302(5911):832–837. doi: 10.1038/302832a0. [DOI] [PubMed] [Google Scholar]
  3. Barker L. A., Ebersole B. J. Histamine H2-receptors on guinea-pig ileum myenteric plexus neurons mediate the release of contractile agents. J Pharmacol Exp Ther. 1982 Apr;221(1):69–75. [PubMed] [Google Scholar]
  4. Barker L. A., Hough L. B. Selectivity of 4-methylhistamine at H1- and H2-receptors in the guinea-pig isolated ileum. Br J Pharmacol. 1983 Sep;80(1):65–71. doi: 10.1111/j.1476-5381.1983.tb11050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berridge M. J., Downes C. P., Hanley M. R. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J. 1982 Sep 15;206(3):587–595. doi: 10.1042/bj2060587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Berridge M. J. Phosphatidylinositol hydrolysis: a multifunctional transducing mechanism. Mol Cell Endocrinol. 1981 Nov;24(2):115–140. doi: 10.1016/0303-7207(81)90055-1. [DOI] [PubMed] [Google Scholar]
  9. Berridge M. J. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J. 1983 Jun 15;212(3):849–858. doi: 10.1042/bj2120849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bolton T. B., Clark J. P. Effects of histamine, high potassium and carbachol on 42K efflux from longitudinal muscle of guinea-pig intestine. J Physiol. 1981 Nov;320:347–361. doi: 10.1113/jphysiol.1981.sp013954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bolton T. B., Clark J. P., Kitamura K., Lang R. J. Evidence that histamine and carbachol may open the same ion channels in longitudinal smooth muscle of guinea-pig ileum. J Physiol. 1981 Nov;320:363–379. doi: 10.1113/jphysiol.1981.sp013955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  13. Bone E. A., Fretten P., Palmer S., Kirk C. J., Michell R. H. Rapid accumulation of inositol phosphates in isolated rat superior cervical sympathetic ganglia exposed to V1-vasopressin and muscarinic cholinergic stimuli. Biochem J. 1984 Aug 1;221(3):803–811. doi: 10.1042/bj2210803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Brown E., Kendall D. A., Nahorski S. R. Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterisation. J Neurochem. 1984 May;42(5):1379–1387. doi: 10.1111/j.1471-4159.1984.tb02798.x. [DOI] [PubMed] [Google Scholar]
  15. Burgess G. M., Godfrey P. P., McKinney J. S., Berridge M. J., Irvine R. F., Putney J. W., Jr The second messenger linking receptor activation to internal Ca release in liver. Nature. 1984 May 3;309(5963):63–66. doi: 10.1038/309063a0. [DOI] [PubMed] [Google Scholar]
  16. Casteels R., Raeymaekers L. The action of acetylcholine and catecholamines on an intracellular calcium store in the smooth muscle cells of the guinea-pig taenia coli. J Physiol. 1979 Sep;294:51–68. doi: 10.1113/jphysiol.1979.sp012914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Daum P. R., Downes C. P., Young J. M. Histamine stimulation of inositol 1-phosphate accumulation in lithium-treated slices from regions of guinea pig brain. J Neurochem. 1984 Jul;43(1):25–32. doi: 10.1111/j.1471-4159.1984.tb06674.x. [DOI] [PubMed] [Google Scholar]
  18. Daum P. R., Downes C. P., Young J. M. Histamine-induced inositol phospholipid breakdown mirrors H1-receptor density in brain. Eur J Pharmacol. 1983 Mar 4;87(4):497–498. doi: 10.1016/0014-2999(83)90092-4. [DOI] [PubMed] [Google Scholar]
  19. Daum P. R., Hill S. J., Young J. M. Histamine H1-agonist potentiation of adenosine-stimulated cyclic AMP accumulation in slices of guinea-pig cerebral cortex: comparison of response and binding parameters. Br J Pharmacol. 1982 Oct;77(2):347–357. doi: 10.1111/j.1476-5381.1982.tb09304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. DeLean A., Munson P. J., Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978 Aug;235(2):E97–102. doi: 10.1152/ajpendo.1978.235.2.E97. [DOI] [PubMed] [Google Scholar]
  21. Durant G. J., Ganellin C. R., Parsons M. E. Chemical differentiation of histamine H1- and H2-receptor agonists. J Med Chem. 1975 Sep;18(9):905–909. doi: 10.1021/jm00243a009. [DOI] [PubMed] [Google Scholar]
  22. Hill S. J., Young J. M. Characterization of [3H]mepyramine binding to the longitudinal muscle of guinea pig small intestine. Mol Pharmacol. 1981 May;19(3):379–387. [PubMed] [Google Scholar]
  23. Hill S. J., Young J. M., Marrian D. H. Specific binding of 3H-mepyramine to histamine H1 receptors in intestinal smooth muscle. Nature. 1977 Nov 24;270(5635):361–363. doi: 10.1038/270361a0. [DOI] [PubMed] [Google Scholar]
  24. Jafferji S. S., Michell R. H. Effects of calcium-antagonistic drugs on the stimulation by carbamoylcholine and histamine of phosphatidylinositol turnover in longitudinal smooth muscle of guinea-pig ileum. Biochem J. 1976 Nov 15;160(2):163–169. doi: 10.1042/bj1600163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jafferji S. S., Michell R. H. Stimulation of phosphatidylinositol turnover by histamine, 5-hydroxytryptamine and adrenaline in the longitudinal smooth muscle of guinea pig ileum. Biochem Pharmacol. 1976 Jun 15;25(12):1429–1430. doi: 10.1016/0006-2952(76)90115-5. [DOI] [PubMed] [Google Scholar]
  26. Michell R. H. Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta. 1975 Mar 25;415(1):81–47. doi: 10.1016/0304-4157(75)90017-9. [DOI] [PubMed] [Google Scholar]
  27. Michell R. H., Kirk C. J., Jones L. M., Downes C. P., Creba J. A. The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: defined characteristics and unanswered questions. Philos Trans R Soc Lond B Biol Sci. 1981 Dec 18;296(1080):123–138. doi: 10.1098/rstb.1981.0177. [DOI] [PubMed] [Google Scholar]
  28. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  29. PATON W. D., RANG H. P. THE UPTAKE OF ATROPINE AND RELATED DRUGS BY INTESTINAL SMOOTH MUSCLE OF THE GUINEA-PIG IN RELATION TO ACETYLCHOLINE RECEPTORS. Proc R Soc Lond B Biol Sci. 1965 Aug 24;163:1–44. doi: 10.1098/rspb.1965.0058. [DOI] [PubMed] [Google Scholar]
  30. Putney J. W., Jr Recent hypotheses regarding the phosphatidylinositol effect. Life Sci. 1981 Sep 21;29(12):1183–1194. doi: 10.1016/0024-3205(81)90221-6. [DOI] [PubMed] [Google Scholar]
  31. RANG H. P. STIMULANT ACTIONS OF VOLATILE ANAESTHETICS ON SMOOTH MUSCLE. Br J Pharmacol Chemother. 1964 Apr;22:356–365. doi: 10.1111/j.1476-5381.1964.tb02040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rubin R. P., Sink L. E., Freer R. J. On the relationship between formylmethionyl-leucyl-phenylalanine stimulation of arachidonyl phosphatidylinositol turnover and lysosomal enzyme secretion by rabbit neutrophils. Mol Pharmacol. 1981 Jan;19(1):31–37. [PubMed] [Google Scholar]
  33. Streb H., Irvine R. F., Berridge M. J., Schulz I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983 Nov 3;306(5938):67–69. doi: 10.1038/306067a0. [DOI] [PubMed] [Google Scholar]
  34. Takayanagi I., Hongo T., Kasuya Y. Difference in the mechanisms by which acetylcholine and histamine interact with Ca2+ to contract the rabbit taenia coli. J Pharm Pharmacol. 1977 Dec;29(12):775–776. doi: 10.1111/j.2042-7158.1977.tb11463.x. [DOI] [PubMed] [Google Scholar]
  35. Watson S. P., Downes C. P. Substance P induced hydrolysis of inositol phospholipids in guinea-pig ileum and rat hypothalamus. Eur J Pharmacol. 1983 Sep 30;93(3-4):245–253. doi: 10.1016/0014-2999(83)90144-9. [DOI] [PubMed] [Google Scholar]
  36. Zilletti L., Franchi-Micheli S., Rosselli P. Uptake and metabolism of histamine in guinea pig ileal longitudinal muscle. Agents Actions. 1978 Oct;8(5):462–469. doi: 10.1007/BF02111429. [DOI] [PubMed] [Google Scholar]

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

RESOURCES