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. 1991 Nov;104(3):639–644. doi: 10.1111/j.1476-5381.1991.tb12482.x

Contraction of vascular smooth muscle induced by phorbol 12,13 dibutyrate in human and rat pulmonary arteries.

J P Savineau 1, R Marthan 1, H Crevel 1
PMCID: PMC1908228  PMID: 1724628

Abstract

1. The effect of phorbol 12,13 dibutyrate (PDB) on vascular tone was studied in both human and rat isolated pulmonary arterial strips (HPA and RPA, respectively). 2. PDB (1 nM to 2 microM) produced slowly developing, sustained and concentration-dependent contractions in HPA (mean EC50 = 3.5 nM, n = 5) and RPA (mean EC50 = 120 nM, n = 5). The maximal response was 185.6 +/- 25% and 207 +/- 27.5% (n = 5) of that induced by K(+)-rich (80mM) solution, and 223 +/- 34.5% and 176.5 +/- 38.6% of the noradrenaline (10 microM)-induced contraction in HPA and RPA, respectively. 3. PDB-induced contractions were not altered either by the presence of atropine (10 microM), propranolol (5 microM), phentolamine (5 microM) or tetrodotoxin (10 microM) in the bathing solution, or by the removal of endothelium from pulmonary arteries. 4. In HPA, the amplitude of PDB-induced contractions was significantly reduced by removal of external calcium ions, addition of verapamil (10 microM) or trifluoperazine (TFP, 5 microM) and significantly increased by Bay K 8644 (0.5 microM). In contrast, in RPA, calcium-free solution and verapamil had only a moderate effect on the maximal PDB-induced contraction (approximately 20% reduction), whereas Bay K 8644 and TFP had no significant effect. In both HPA and RPA, PDB-contractions in calcium-free solutions were not modified by ryanodine (25 microM) or by 8-(N,N diethylamino)octyl-3,4,5, trimethoxybenzoate hydrochloride (TMB-8, 50 microM). 5. PDB-induced contractions were inhibited by protein kinase C (PKC) antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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  1. Abdel-Latif A. A. Calcium-mobilizing receptors, polyphosphoinositides, and the generation of second messengers. Pharmacol Rev. 1986 Sep;38(3):227–272. [PubMed] [Google Scholar]
  2. Adelstein R. S., Hathaway D. R. Role of calcium and cyclic adenosine 3':5' monophosphate in regulating smooth muscle contraction. Mechanisms of excitation-contraction coupling in smooth muscle. Am J Cardiol. 1979 Oct 22;44(5):783–787. doi: 10.1016/0002-9149(79)90197-8. [DOI] [PubMed] [Google Scholar]
  3. Asano M., Suzuki Y., Hidaka H. Effects of various calmodulin antagonists on contraction of rabbit aortic strips. J Pharmacol Exp Ther. 1982 Jan;220(1):191–196. [PubMed] [Google Scholar]
  4. Auguet M., Delaflotte S., Chabrier P. E., Braquet P. Comparative effects of endothelin and phorbol 12-13 dibutyrate in rat aorta. Life Sci. 1989;45(21):2051–2059. doi: 10.1016/0024-3205(89)90580-8. [DOI] [PubMed] [Google Scholar]
  5. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  6. Chatterjee M., Tejada M. Phorbol ester-induced contraction in chemically skinned vascular smooth muscle. Am J Physiol. 1986 Sep;251(3 Pt 1):C356–C361. doi: 10.1152/ajpcell.1986.251.3.C356. [DOI] [PubMed] [Google Scholar]
  7. Chiou C. Y., Malagodi M. H. Studies on the mechanism of action of a new Ca-2+ antagonist, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride in smooth and skeletal muscles. Br J Pharmacol. 1975 Feb;53(2):279–285. doi: 10.1111/j.1476-5381.1975.tb07359.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chiu P. J., Tetzloff G., Chatterjee M., Sybertz E. J. Phorbol 12,13-dibutyrate, an activator of protein kinase C, stimulates both contraction and Ca2+ fluxes in dog saphenous vein. Naunyn Schmiedebergs Arch Pharmacol. 1988 Aug;338(2):114–120. doi: 10.1007/BF00174857. [DOI] [PubMed] [Google Scholar]
  9. Fish R. D., Sperti G., Colucci W. S., Clapham D. E. Phorbol ester increases the dihydropyridine-sensitive calcium conductance in a vascular smooth muscle cell line. Circ Res. 1988 May;62(5):1049–1054. doi: 10.1161/01.res.62.5.1049. [DOI] [PubMed] [Google Scholar]
  10. Forder J., Scriabine A., Rasmussen H. Plasma membrane calcium flux, protein kinase C activation and smooth muscle contraction. J Pharmacol Exp Ther. 1985 Nov;235(2):267–273. [PubMed] [Google Scholar]
  11. Gschwendt M., Horn F., Kittstein W., Fürstenberger G., Besemfelder E., Marks F. Calcium and phospholipid-dependent protein kinase activity in mouse epidermis cytosol. Stimulation by complete and incomplete tumor promoters and inhibition by various compounds. Biochem Biophys Res Commun. 1984 Oct 15;124(1):63–68. doi: 10.1016/0006-291x(84)90916-1. [DOI] [PubMed] [Google Scholar]
  12. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  13. Himpens B., Matthijs G., Somlyo A. V., Butler T. M., Somlyo A. P. Cytoplasmic free calcium, myosin light chain phosphorylation, and force in phasic and tonic smooth muscle. J Gen Physiol. 1988 Dec;92(6):713–729. doi: 10.1085/jgp.92.6.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hwang K. S., van Breemen C. Ryanodine modulation of 45Ca efflux and tension in rabbit aortic smooth muscle. Pflugers Arch. 1987 Apr;408(4):343–350. doi: 10.1007/BF00581127. [DOI] [PubMed] [Google Scholar]
  15. Ikebe M., Inagaki M., Kanamaru K., Hidaka H. Phosphorylation of smooth muscle myosin light chain kinase by Ca2+-activated, phospholipid-dependent protein kinase. J Biol Chem. 1985 Apr 25;260(8):4547–4550. [PubMed] [Google Scholar]
  16. Jiang M. J., Morgan K. G. Agonist-specific myosin phosphorylation and intracellular calcium during isometric contractions of arterial smooth muscle. Pflugers Arch. 1989 Apr;413(6):637–643. doi: 10.1007/BF00581814. [DOI] [PubMed] [Google Scholar]
  17. Jiang M. J., Morgan K. G. Intracellular calcium levels in phorbol ester-induced contractions of vascular muscle. Am J Physiol. 1987 Dec;253(6 Pt 2):H1365–H1371. doi: 10.1152/ajpheart.1987.253.6.H1365. [DOI] [PubMed] [Google Scholar]
  18. Kamm K. E., Stull J. T. The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol. 1985;25:593–620. doi: 10.1146/annurev.pa.25.040185.003113. [DOI] [PubMed] [Google Scholar]
  19. Kariya K., Takai Y. Distinct functions of down-regulation-sensitive and -resistant types of protein kinase C in rabbit aortic smooth muscle cells. FEBS Lett. 1987 Jul 13;219(1):119–124. doi: 10.1016/0014-5793(87)81202-4. [DOI] [PubMed] [Google Scholar]
  20. Kikkawa U., Takai Y., Tanaka Y., Miyake R., Nishizuka Y. Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters. J Biol Chem. 1983 Oct 10;258(19):11442–11445. [PubMed] [Google Scholar]
  21. Kuo J. F., Andersson R. G., Wise B. C., Mackerlova L., Salomonsson I., Brackett N. L., Katoh N., Shoji M., Wrenn R. W. Calcium-dependent protein kinase: widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipid, calmodulin, and trifluoperazine. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7039–7043. doi: 10.1073/pnas.77.12.7039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Levin R. M., Weiss B. Binding of trifluoperazine to the calcium-dependent activator of cyclic nucleotide phosphodiesterase. Mol Pharmacol. 1977 Jul;13(4):690–697. [PubMed] [Google Scholar]
  23. Loirand G., Pacaud P., Mironneau C., Mironneau J. GTP-binding proteins mediate noradrenaline effects on calcium and chloride currents in rat portal vein myocytes. J Physiol. 1990 Sep;428:517–529. doi: 10.1113/jphysiol.1990.sp018225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Murphy R. A., Aksoy M. O., Dillon P. F., Gerthoffer W. T., Kamm K. E. The role of myosin light chain phosphorylation in regulation of the cross-bridge cycle. Fed Proc. 1983 Jan;42(1):51–56. [PubMed] [Google Scholar]
  25. Nishimura J., Khalil R. A., Drenth J. P., van Breemen C. Evidence for increased myofilament Ca2+ sensitivity in norepinephrine-activated vascular smooth muscle. Am J Physiol. 1990 Jul;259(1 Pt 2):H2–H8. doi: 10.1152/ajpheart.1990.259.1.H2. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Pfeilschifter J., Ochsner M., Whitebread S., De Gasparo M. Down-regulation of protein kinase C potentiates angiotensin II-stimulated polyphosphoinositide hydrolysis in vascular smooth-muscle cells. Biochem J. 1989 Aug 15;262(1):285–291. doi: 10.1042/bj2620285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rasmussen H., Takuwa Y., Park S. Protein kinase C in the regulation of smooth muscle contraction. FASEB J. 1987 Sep;1(3):177–185. [PubMed] [Google Scholar]
  29. Rogers T. B., Gaa S. T., Massey C., Dösemeci A. Protein kinase C inhibits Ca2+ accumulation in cardiac sarcoplasmic reticulum. J Biol Chem. 1990 Mar 15;265(8):4302–4308. [PubMed] [Google Scholar]
  30. Salaices M., Balfagon G., Arribas S., de Sagarra M. R., Marín J. Effects of phorbol 12,13-dibutyrate on the vascular tone and on norepinephrine- and potassium-induced contractions of cat cerebral arteries. J Pharmacol Exp Ther. 1990 Oct;255(1):66–73. [PubMed] [Google Scholar]
  31. Savineau J. P., Mironneau J., Mironneau C. Contractile properties of chemically skinned fibers from pregnant rat myometrium: existence of an internal Ca-store. Pflugers Arch. 1988 Mar;411(3):296–303. doi: 10.1007/BF00585118. [DOI] [PubMed] [Google Scholar]
  32. Sawamura M., Kobayashi Y., Nara Y., Hattori K., Yamori Y. Effect of extracellular calcium on vascular contraction induced by phorbol ester. Biochem Biophys Res Commun. 1987 May 29;145(1):494–501. doi: 10.1016/0006-291x(87)91348-9. [DOI] [PubMed] [Google Scholar]
  33. Secrest R. J., Lucaites V. L., Mendelsohn L. G., Cohen M. L. Protein kinase C translocation in rat stomach fundus: effects of serotonin, carbamylcholine and phorbol dibutyrate. J Pharmacol Exp Ther. 1991 Jan;256(1):103–109. [PubMed] [Google Scholar]
  34. Singer H. A. Phorbol ester-induced stress and myosin light chain phosphorylation in swine carotid medial smooth muscle. J Pharmacol Exp Ther. 1990 Mar;252(3):1068–1074. [PubMed] [Google Scholar]
  35. Spedding M. Interaction of phorbol esters with Ca2+ channels in smooth muscle. Br J Pharmacol. 1987 Jun;91(2):377–384. doi: 10.1111/j.1476-5381.1987.tb10292.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tamaoki T., Nomoto H., Takahashi I., Kato Y., Morimoto M., Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):397–402. doi: 10.1016/0006-291x(86)90008-2. [DOI] [PubMed] [Google Scholar]
  37. Wolf M., LeVine H., 3rd, May W. S., Jr, Cuatrecasas P., Sahyoun N. A model for intracellular translocation of protein kinase C involving synergism between Ca2+ and phorbol esters. Nature. 1985 Oct 10;317(6037):546–549. doi: 10.1038/317546a0. [DOI] [PubMed] [Google Scholar]

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