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. 1992 Apr;105(4):997–1003. doi: 10.1111/j.1476-5381.1992.tb09091.x

Comparative effects of BRL 38227, nitrendipine and isoprenaline on carbachol- and histamine-stimulated phosphoinositide metabolism in airway smooth muscle.

R A Challiss 1, N Patel 1, J R Arch 1
PMCID: PMC1908721  PMID: 1324062

Abstract

1. The ability of BRL 38227 and nitrendipine to affect muscarinic agonist and histamine-stimulated [3H]-inositol phosphate accumulation in slices of bovine tracheal smooth muscle has been studied and compared with the established inhibitory effects of isoprenaline on this pathway. 2. Pre-addition of BRL 38227 (5 microM), nitrendipine (1 microM) or isoprenaline (10 microM) significantly inhibited the subsequent inositol phosphate response to histamine at all concentrations studied (10- 1000 microM). BRL 38227 and nitrendipine also significantly inhibited the [3H]-inositol phosphate response to low (1 microM), but not high (100 microM) concentrations of carbachol. Isoprenaline had no effect at any concentration of carbachol studied. 3. Nitrendipine (IC50 = 95 nM) and BRL 38227 (IC50 = 322 nM) caused concentration-related inhibitions of the inositol phosphate response to histamine (100 microM). Similar maximal inhibitions were caused by each agent (55-58%). Inhibitory effect of BRL 38227 was reduced in potency (IC50 = 5.5 microM), but not magnitude, in the presence of glibenclamide (0.5 microM). 4. Time-course studies comparing the effects of BRL 38227 addition 15 min before, and 10 min after histamine challenge showed that for pre-addition a distinct (less than 2 min) lag occurred following histamine addition before the inhibitory effect of BRL 38227 was manifest. In contrast, when BRL 38227 was added 10 min after histamine, an inhibitory effect was immediately apparent. 5. Further evidence for an initial, 'protected' phase of inositol phosphate accumulation was provided by the finding that BRL 38227 pre-addition had no effect on the early (0-300 s) time-course of inositol 1,4,5-trisphosphate mass accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Allen S. L., Beech D. J., Foster R. W., Morgan G. P., Small R. C. Electrophysiological and other aspects of the relaxant action of isoprenaline in guinea-pig isolated trachealis. Br J Pharmacol. 1985 Dec;86(4):843–854. doi: 10.1111/j.1476-5381.1985.tb11106.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen S. L., Boyle J. P., Cortijo J., Foster R. W., Morgan G. P., Small R. C. Electrical and mechanical effects of BRL34915 in guinea-pig isolated trachealis. Br J Pharmacol. 1986 Oct;89(2):395–405. doi: 10.1111/j.1476-5381.1986.tb10273.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andersson R. G., Kövesi G., Ericsson E. Beta-adrenoceptor stimulation and cyclic AMP levels in bovine tracheal muscle of old and young animals. Acta Pharmacol Toxicol (Copenh) 1978 Oct;43(4):323–327. doi: 10.1111/j.1600-0773.1978.tb02273.x. [DOI] [PubMed] [Google Scholar]
  4. Arch J. R., Buckle D. R., Bumstead J., Clarke G. D., Taylor J. F., Taylor S. G. Evaluation of the potassium channel activator cromakalim (BRL 34915) as a bronchodilator in the guinea-pig: comparison with nifedipine. Br J Pharmacol. 1988 Nov;95(3):763–770. doi: 10.1111/j.1476-5381.1988.tb11702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ashwood V. A., Buckingham R. E., Cassidy F., Evans J. M., Faruk E. A., Hamilton T. C., Nash D. J., Stemp G., Willcocks K. Synthesis and antihypertensive activity of 4-(cyclic amido)-2H-1-benzopyrans. J Med Chem. 1986 Nov;29(11):2194–2201. doi: 10.1021/jm00161a011. [DOI] [PubMed] [Google Scholar]
  6. Baron C. B., Cunningham M., Strauss J. F., 3rd, Coburn R. F. Pharmacomechanical coupling in smooth muscle may involve phosphatidylinositol metabolism. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6899–6903. doi: 10.1073/pnas.81.21.6899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Berry J. L., Elliott K. R., Foster R. W., Green K. A., Murray M. A., Small R. C. Mechanical, biochemical and electrophysiological studies of RP 49356 and cromakalim in guinea-pig and bovine trachealis muscle. Pulm Pharmacol. 1991;4(2):91–98. doi: 10.1016/0952-0600(91)90058-b. [DOI] [PubMed] [Google Scholar]
  8. Black J. L., Armour C. L., Johnson P. R., Alouan L. A., Barnes P. J. The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1384–1389. doi: 10.1164/ajrccm/142.6_Pt_1.1384. [DOI] [PubMed] [Google Scholar]
  9. Bowring N. E., Buckle D. R., Clarke G. D., Taylor J. F., Arch J. R. Evaluation of the potassium channel activator BRL 38227 as an inhaled bronchodilator in the guinea-pig: contrast with nifedipine and salbutamol. Pulm Pharmacol. 1991;4(2):99–105. doi: 10.1016/0952-0600(91)90059-c. [DOI] [PubMed] [Google Scholar]
  10. Bray K. M., Weston A. H., Duty S., Newgreen D. T., Longmore J., Edwards G., Brown T. J. Differences between the effects of cromakalim and nifedipine on agonist-induced responses in rabbit aorta. Br J Pharmacol. 1991 Feb;102(2):337–344. doi: 10.1111/j.1476-5381.1991.tb12175.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Buckingham R. E., Hamilton T. C., Howlett D. R., Mootoo S., Wilson C. Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat. Br J Pharmacol. 1989 May;97(1):57–64. doi: 10.1111/j.1476-5381.1989.tb11923.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Challiss R. A., Batty I. H., Nahorski S. R. Mass measurements of inositol(1,4,5)trisphosphate in rat cerebral cortex slices using a radioreceptor assay: effects of neurotransmitters and depolarization. Biochem Biophys Res Commun. 1988 Dec 15;157(2):684–691. doi: 10.1016/s0006-291x(88)80304-8. [DOI] [PubMed] [Google Scholar]
  13. Chilvers E. R., Barnes P. J., Nahorski S. R. Characterization of agonist-stimulated incorporation of myo-[3H]inositol into inositol phospholipids and [3H]inositol phosphate formation in tracheal smooth muscle. Biochem J. 1989 Sep 15;262(3):739–746. doi: 10.1042/bj2620739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chilvers E. R., Batty I. H., Barnes P. J., Nahorski S. R. Formation of inositol polyphosphates in airway smooth muscle after muscarinic receptor stimulation. J Pharmacol Exp Ther. 1990 Feb;252(2):786–791. [PubMed] [Google Scholar]
  15. Chilvers E. R., Batty I. H., Challiss R. A., Barnes P. J., Nahorski S. R. Determination of mass changes in phosphatidylinositol 4,5-bisphosphate and evidence for agonist-stimulated metabolism of inositol 1,4,5-trisphosphate in airway smooth muscle. Biochem J. 1991 Apr 15;275(Pt 2):373–379. doi: 10.1042/bj2750373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Chilvers E. R., Challiss R. A., Barnes P. J., Nahorski S. R. Mass changes of inositol(1,4,5)trisphosphate in trachealis muscle following agonist stimulation. Eur J Pharmacol. 1989 May 30;164(3):587–590. doi: 10.1016/0014-2999(89)90269-0. [DOI] [PubMed] [Google Scholar]
  17. Clapham J. C., Wilson C. Anti-spasmogenic and spasmolytic effects of BRL 34915: a comparison with nifedipine and nicorandil. J Auton Pharmacol. 1987 Sep;7(3):233–242. doi: 10.1111/j.1474-8673.1987.tb00152.x. [DOI] [PubMed] [Google Scholar]
  18. Coburn R. F., Baron C. B. Coupling mechanisms in airway smooth muscle. Am J Physiol. 1990 Apr;258(4 Pt 1):L119–L133. doi: 10.1152/ajplung.1990.258.4.L119. [DOI] [PubMed] [Google Scholar]
  19. Cook N. S., Weir S. W., Danzeisen M. C. Anti-vasoconstrictor effects of the K+ channel opener cromakalim on the rabbit aorta--comparison with the calcium antagonist isradipine. Br J Pharmacol. 1988 Nov;95(3):741–752. doi: 10.1111/j.1476-5381.1988.tb11700.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. Downes C. P., Wusteman M. M. Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands. Biochem J. 1983 Dec 15;216(3):633–640. doi: 10.1042/bj2160633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Eberhard D. A., Holz R. W. Intracellular Ca2+ activates phospholipase C. Trends Neurosci. 1988 Dec;11(12):517–520. doi: 10.1016/0166-2236(88)90174-9. [DOI] [PubMed] [Google Scholar]
  23. Gillespie J. S., Sheng H. The lack of involvement of cyclic nucleotides in the smooth muscle relaxant action of BRL 34915. Br J Pharmacol. 1988 Aug;94(4):1189–1197. doi: 10.1111/j.1476-5381.1988.tb11638.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gopalakrishnan M., Johnson D. E., Janis R. A., Triggle D. J. Characterization of binding of the ATP-sensitive potassium channel ligand, [3H]glyburide, to neuronal and muscle preparations. J Pharmacol Exp Ther. 1991 Jun;257(3):1162–1171. [PubMed] [Google Scholar]
  25. Gunst S. J., Stropp J. Q., Flavahan N. A. Muscarinic receptor reserve and beta-adrenergic sensitivity in tracheal smooth muscle. J Appl Physiol (1985) 1989 Sep;67(3):1294–1298. doi: 10.1152/jappl.1989.67.3.1294. [DOI] [PubMed] [Google Scholar]
  26. Hall I. P., Donaldson J., Hill S. J. Inhibition of histamine-stimulated inositol phospholipid hydrolysis by agents which increase cyclic AMP levels in bovine tracheal smooth muscle. Br J Pharmacol. 1989 Jun;97(2):603–613. doi: 10.1111/j.1476-5381.1989.tb11992.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hall I. P., Donaldson J., Hill S. J. Modulation of carbachol-induced inositol phosphate formation in bovine tracheal smooth muscle by cyclic AMP phosphodiesterase inhibitors. Biochem Pharmacol. 1990 Apr 15;39(8):1357–1363. doi: 10.1016/0006-2952(90)90013-b. [DOI] [PubMed] [Google Scholar]
  28. Hall I. P., Hill S. J. Beta-adrenoceptor stimulation inhibits histamine-stimulated inositol phospholipid hydrolysis in bovine tracheal smooth muscle. Br J Pharmacol. 1988 Dec;95(4):1204–1212. doi: 10.1111/j.1476-5381.1988.tb11757.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hamilton T. C., Weston A. H. Cromakalim, nicorandil and pinacidil: novel drugs which open potassium channels in smooth muscle. Gen Pharmacol. 1989;20(1):1–9. doi: 10.1016/0306-3623(89)90052-9. [DOI] [PubMed] [Google Scholar]
  30. Hashimoto T., Hirata M., Ito Y. A role for inositol 1,4,5-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle. Br J Pharmacol. 1985 Sep;86(1):191–199. doi: 10.1111/j.1476-5381.1985.tb09449.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Honda K., Satake T., Takagi K., Tomita T. Effects of relaxants on electrical and mechanical activities in the guinea-pig tracheal muscle. Br J Pharmacol. 1986 Apr;87(4):665–671. doi: 10.1111/j.1476-5381.1986.tb14583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ito S., Kajikuri J., Itoh T., Kuriyama H. Effects of lemakalim on changes in Ca2+ concentration and mechanical activity induced by noradrenaline in the rabbit mesenteric artery. Br J Pharmacol. 1991 Sep;104(1):227–233. doi: 10.1111/j.1476-5381.1991.tb12411.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jenne J. W., Shaughnessy T. K., Druz W. S., Manfredi C. J., Vestal R. E. In vivo functional antagonism between isoproterenol and bronchoconstrictants in the dog. J Appl Physiol (1985) 1987 Aug;63(2):812–819. doi: 10.1152/jappl.1987.63.2.812. [DOI] [PubMed] [Google Scholar]
  34. Katsuyama H., Suzuki S., Nishiye E. Actions of second messengers synthesized by various spasmogenic agents and their relation to mechanical responses in dog tracheal smooth muscle. Br J Pharmacol. 1990 May;100(1):41–48. doi: 10.1111/j.1476-5381.1990.tb12049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kume H., Takai A., Tokuno H., Tomita T. Regulation of Ca2+-dependent K+-channel activity in tracheal myocytes by phosphorylation. Nature. 1989 Sep 14;341(6238):152–154. doi: 10.1038/341152a0. [DOI] [PubMed] [Google Scholar]
  36. Madison J. M., Brown J. K. Differential inhibitory effects of forskolin, isoproterenol, and dibutyryl cyclic adenosine monophosphate on phosphoinositide hydrolysis in canine tracheal smooth muscle. J Clin Invest. 1988 Oct;82(4):1462–1465. doi: 10.1172/JCI113752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Meurs H., Roffel A. F., Postema J. B., Timmermans A., Elzinga C. R., Kauffman H. F., Zaagsma J. Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists. Eur J Pharmacol. 1988 Nov 1;156(2):271–274. doi: 10.1016/0014-2999(88)90331-7. [DOI] [PubMed] [Google Scholar]
  38. Murray M. A., Boyle J. P., Small R. C. Cromakalim-induced relaxation of guinea-pig isolated trachealis: antagonism by glibenclamide and by phentolamine. Br J Pharmacol. 1989 Nov;98(3):865–874. doi: 10.1111/j.1476-5381.1989.tb14615.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Murray R. K., Bennett C. F., Fluharty S. J., Kotlikoff M. I. Mechanism of phorbol ester inhibition of histamine-induced IP3 formation in cultured airway smooth muscle. Am J Physiol. 1989 Oct;257(4 Pt 1):L209–L216. doi: 10.1152/ajplung.1989.257.4.L209. [DOI] [PubMed] [Google Scholar]
  40. Murray R. K., Kotlikoff M. I. Receptor-activated calcium influx in human airway smooth muscle cells. J Physiol. 1991 Apr;435:123–144. doi: 10.1113/jphysiol.1991.sp018501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Offer G. J., Chilvers E. R., Nahorski S. R. Beta-adrenoceptor induced inhibition of muscarinic receptor-stimulated phosphoinositide metabolism is agonist specific in bovine tracheal smooth muscle. Eur J Pharmacol. 1991 Jul 12;207(3):243–248. doi: 10.1016/0922-4106(91)90036-h. [DOI] [PubMed] [Google Scholar]
  42. Polson J. B., Krzanowski J. J., Szentivanyi A. Inhibition of a high affinity cyclic AMP phosphodiesterase and relaxation of canine tracheal smooth muscle. Biochem Pharmacol. 1982 Nov 1;31(21):3403–3406. doi: 10.1016/0006-2952(82)90618-9. [DOI] [PubMed] [Google Scholar]
  43. Raeburn D., Brown T. J. RP 49356 and cromakalim relax airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel: a comparison with nifedipine. J Pharmacol Exp Ther. 1991 Feb;256(2):480–485. [PubMed] [Google Scholar]
  44. Rasmussen H., Kelley G., Douglas J. S. Interactions between Ca2+ and cAMP messenger system in regulation of airway smooth muscle contraction. Am J Physiol. 1990 Jun;258(6 Pt 1):L279–L288. doi: 10.1152/ajplung.1990.258.6.L279. [DOI] [PubMed] [Google Scholar]
  45. Takuwa Y., Takuwa N., Rasmussen H. Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol, and phosphatidic acid. J Biol Chem. 1986 Nov 5;261(31):14670–14675. [PubMed] [Google Scholar]
  46. Torphy T. J. Differential relaxant effects of isoproterenol on methacholine- versus leukotriene D4-induced contraction in the guinea-pig trachea. Eur J Pharmacol. 1984 Jul 20;102(3-4):549–553. doi: 10.1016/0014-2999(84)90580-6. [DOI] [PubMed] [Google Scholar]
  47. Van Amsterdam R. G., Meurs H., Brouwer F., Postema J. B., Timmermans A., Zaagsma J. Role of phosphoinositide metabolism in functional antagonism of airway smooth muscle contraction by beta-adrenoceptor agonists. Eur J Pharmacol. 1989 May 11;172(2):175–183. doi: 10.1016/0922-4106(89)90008-4. [DOI] [PubMed] [Google Scholar]
  48. Worley J. F., 3rd, Kotlikoff M. I. Dihydropyridine-sensitive single calcium channels in airway smooth muscle cells. Am J Physiol. 1990 Dec;259(6 Pt 1):L468–L480. doi: 10.1152/ajplung.1990.259.6.L468. [DOI] [PubMed] [Google Scholar]

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