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. 1996 Jan;117(1):175–183. doi: 10.1111/j.1476-5381.1996.tb15171.x

Investigation of the effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) on membrane currents in rat portal vein.

A J Kirkup 1, G Edwards 1, A H Weston 1
PMCID: PMC1909371  PMID: 8825360

Abstract

1. The effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) were investigated on evoked and spontaneous currents in freshly-isolated cells from the rat portal vein by use of conventional whole-cell recording and perforated-patch techniques. 2. At a holding potential of -60 mV in potassium-free, caesium-containing solutions, NPPB (10 microM) inhibited calcium (Ca)-sensitive chloride currents (ICl(Ca)) evoked by caffeine (10 mM) and by noradrenaline (10 microM) by 58% and 96%, respectively. 3. At a holding potential of -2 mV in potassium (K)-containing solutions, NPPB (10 microM) inhibited charybdotoxin-sensitive K-currents (IBK(Ca)) induced by noradrenaline (10 microM) and acetylcholine (10 microM) by approximately 90%. In contrast, IBK(Ca) induced by caffeine (10 mM) was unaffected in the presence of NPPB (10 microM). Conversely, IBK(Ca) elicited by caffeine (2 mM) was reduced by approximately 50% whereas IBK(Ca) evoked by noradrenaline (50 microM) was not significantly inhibited by NPPB. 4. In K-containing solutions, NPPB (10 microM) abolished spontaneous transient outward currents (STOCs) and induced a slowly-developing outward K-current. Bath application of glibenclamide (10 microM) abolished the outward current but did not antagonize the inhibitory effects of NPPB on STOCs or on IBK(Ca) evoked by noradrenaline. 5. In caesium-containing solutions, NPPB (30 microM) inhibited voltage-sensitive Ca-currents. 6. In Ca-free, K-containing solutions and in the presence of glibenclamide (5 microM), IBK(Ca) induced by 20 microM NS1619 was enhanced by NPPB (10 microM). 7. It is concluded that NPPB inhibits agonist-induced ICl(Ca) in rat portal vein smooth muscle. However, this agent also inhibits agonist-evoked IBK(Ca) and STOCs. Moreover, NPPB inhibits voltage-sensitive Ca-currents and stimulates a glibenclamide-sensitive K-current and IBK(Ca). The effects of this agent on evoked ICl(Ca) and IBK(Ca) and on STOCs probably involves an inhibitory action on intracellular Ca-stores.

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Selected References

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

  1. Aickin C. C., Brading A. F. Measurement of intracellular chloride in guinea-pig vas deferens by ion analysis, 36chloride efflux and micro-electrodes. J Physiol. 1982 May;326:139–154. doi: 10.1113/jphysiol.1982.sp014182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aickin C. C., Vermuë N. A. Microelectrode measurement of intracellular chloride activity in smooth muscle cells of guinea-pig ureter. Pflugers Arch. 1983 Apr;397(1):25–28. doi: 10.1007/BF00585163. [DOI] [PubMed] [Google Scholar]
  3. Amédée T., Benham C. D., Bolton T. B., Byrne N. G., Large W. A. Potassium, chloride and non-selective cation conductances opened by noradrenaline in rabbit ear artery cells. J Physiol. 1990 Apr;423:551–568. doi: 10.1113/jphysiol.1990.sp018039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Amédée T., Large W. A. Microelectrode study on the ionic mechanisms which contribute to the noradrenaline-induced depolarization in isolated cells of the rabbit portal vein. Br J Pharmacol. 1989 Aug;97(4):1331–1337. doi: 10.1111/j.1476-5381.1989.tb12596.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Amédée T., Large W. A., Wang Q. Characteristics of chloride currents activated by noradrenaline in rabbit ear artery cells. J Physiol. 1990 Sep;428:501–516. doi: 10.1113/jphysiol.1990.sp018224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baron A., Pacaud P., Loirand G., Mironneau C., Mironneau J. Pharmacological block of Ca(2+)-activated Cl- current in rat vascular smooth muscle cells in short-term primary culture. Pflugers Arch. 1991 Dec;419(6):553–558. doi: 10.1007/BF00370294. [DOI] [PubMed] [Google Scholar]
  7. Beech D. J., Bolton T. B. Two components of potassium current activated by depolarization of single smooth muscle cells from the rabbit portal vein. J Physiol. 1989 Nov;418:293–309. doi: 10.1113/jphysiol.1989.sp017841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Benham C. D., Bolton T. B. Spontaneous transient outward currents in single visceral and vascular smooth muscle cells of the rabbit. J Physiol. 1986 Dec;381:385–406. doi: 10.1113/jphysiol.1986.sp016333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bolton T. B., Lim S. P. Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine. J Physiol. 1989 Feb;409:385–401. doi: 10.1113/jphysiol.1989.sp017504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Byrne N. G., Large W. A. Action of noradrenaline on single smooth muscle cells freshly dispersed from the rat anococcygeus muscle. J Physiol. 1987 Aug;389:513–525. doi: 10.1113/jphysiol.1987.sp016669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Byrne N. G., Large W. A. Membrane ionic mechanisms activated by noradrenaline in cells isolated from the rabbit portal vein. J Physiol. 1988 Oct;404:557–573. doi: 10.1113/jphysiol.1988.sp017306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Edwards G., Niederste-Hollenberg A., Schneider J., Noack T., Weston A. H. Ion channel modulation by NS 1619, the putative BKCa channel opener, in vascular smooth muscle. Br J Pharmacol. 1994 Dec;113(4):1538–1547. doi: 10.1111/j.1476-5381.1994.tb17171.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Edwards G., Weston A. H. The pharmacology of ATP-sensitive potassium channels. Annu Rev Pharmacol Toxicol. 1993;33:597–637. doi: 10.1146/annurev.pa.33.040193.003121. [DOI] [PubMed] [Google Scholar]
  14. Ehrlich B. E., Bezprozvanny I. Intracellular calcium release channels. Chin J Physiol. 1994;37(1):1–7. [PubMed] [Google Scholar]
  15. Hogg R. C., Wang Q., Helliwell R. M., Large W. A. Properties of spontaneous inward currents in rabbit pulmonary artery smooth muscle cells. Pflugers Arch. 1993 Nov;425(3-4):233–240. doi: 10.1007/BF00374172. [DOI] [PubMed] [Google Scholar]
  16. Hogg R. C., Wang Q., Large W. A. Action of niflumic acid on evoked and spontaneous calcium-activated chloride and potassium currents in smooth muscle cells from rabbit portal vein. Br J Pharmacol. 1994 Jul;112(3):977–984. doi: 10.1111/j.1476-5381.1994.tb13177.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hogg R. C., Wang Q., Large W. A. Effects of Cl channel blockers on Ca-activated chloride and potassium currents in smooth muscle cells from rabbit portal vein. Br J Pharmacol. 1994 Apr;111(4):1333–1341. doi: 10.1111/j.1476-5381.1994.tb14891.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hogg R. C., Wang Q., Large W. A. Time course of spontaneous calcium-activated chloride currents in smooth muscle cells from the rabbit portal vein. J Physiol. 1993 May;464:15–31. doi: 10.1113/jphysiol.1993.sp019622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Horn R., Marty A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol. 1988 Aug;92(2):145–159. doi: 10.1085/jgp.92.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ibbotson T., Edwards G., Noack T., Weston A. H. Effects of P1060 and aprikalim on whole-cell currents in rat portal vein; inhibition by glibenclamide and phentolamine. Br J Pharmacol. 1993 Apr;108(4):991–998. doi: 10.1111/j.1476-5381.1993.tb13496.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Large W. A. Three membrane-conductance mechanisms activated by noradrenaline in vascular smooth muscle. Z Kardiol. 1991;80 (Suppl 7):55–57. [PubMed] [Google Scholar]
  22. Li M., McCann J. D., Welsh M. J. Apical membrane Cl- channels in airway epithelia: anion selectivity and effect of an inhibitor. Am J Physiol. 1990 Aug;259(2 Pt 1):C295–C301. doi: 10.1152/ajpcell.1990.259.2.C295. [DOI] [PubMed] [Google Scholar]
  23. Loirand G., Faiderbe S., Baron A., Geffard M., Mironneau J. Autoanti-phosphatidylinositide antibodies specifically inhibit noradrenaline effects on Ca2+ and Cl- channels in rat portal vein myocytes. J Biol Chem. 1992 Mar 5;267(7):4312–4316. [PubMed] [Google Scholar]
  24. Marty A., Tan Y. P., Trautmann A. Three types of calcium-dependent channel in rat lacrimal glands. J Physiol. 1984 Dec;357:293–325. doi: 10.1113/jphysiol.1984.sp015501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meissner G. Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. Annu Rev Physiol. 1994;56:485–508. doi: 10.1146/annurev.ph.56.030194.002413. [DOI] [PubMed] [Google Scholar]
  26. Noack T., Deitmer P., Edwards G., Weston A. H. Characterization of potassium currents modulated by BRL 38227 in rat portal vein. Br J Pharmacol. 1992 Jul;106(3):717–726. doi: 10.1111/j.1476-5381.1992.tb14400.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ohya Y., Terada K., Yamaguchi K., Inoue R., Okabe K., Kitamura K., Hirata M., Kuriyama H. Effects of inositol phosphates on the membrane activity of smooth muscle cells of the rabbit portal vein. Pflugers Arch. 1988 Sep;412(4):382–389. doi: 10.1007/BF01907556. [DOI] [PubMed] [Google Scholar]
  28. Olesen S. P., Munch E., Moldt P., Drejer J. Selective activation of Ca(2+)-dependent K+ channels by novel benzimidazolone. Eur J Pharmacol. 1994 Jan 4;251(1):53–59. doi: 10.1016/0014-2999(94)90442-1. [DOI] [PubMed] [Google Scholar]
  29. Ottolia M., Toro L. Potentiation of large conductance KCa channels by niflumic, flufenamic, and mefenamic acids. Biophys J. 1994 Dec;67(6):2272–2279. doi: 10.1016/S0006-3495(94)80712-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pacaud P., Loirand G., Baron A., Mironneau C., Mironneau J. Ca2+ channel activation and membrane depolarization mediated by Cl- channels in response to noradrenaline in vascular myocytes. Br J Pharmacol. 1991 Dec;104(4):1000–1006. doi: 10.1111/j.1476-5381.1991.tb12540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pacaud P., Loirand G., Grégoire G., Mironneau C., Mironneau J. Noradrenaline-activated heparin-sensitive Ca2+ entry after depletion of intracellular Ca2+ store in portal vein smooth muscle cells. J Biol Chem. 1993 Feb 25;268(6):3866–3872. [PubMed] [Google Scholar]
  32. Pacaud P., Loirand G., Mironneau C., Mironneau J. Noradrenaline activates a calcium-activated chloride conductance and increases the voltage-dependent calcium current in cultured single cells of rat portal vein. Br J Pharmacol. 1989 May;97(1):139–146. doi: 10.1111/j.1476-5381.1989.tb11934.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pon D. J., Flezar M., Litster D. L., Heisler S. Diphenylamine-2-carboxylate analogues block Cl- conductances in A7r5 cells by affecting cellular Ca2+ homeostasis. Eur J Pharmacol. 1993 Apr 15;245(2):119–127. doi: 10.1016/0922-4106(93)90119-t. [DOI] [PubMed] [Google Scholar]
  34. Rae J., Cooper K., Gates P., Watsky M. Low access resistance perforated patch recordings using amphotericin B. J Neurosci Methods. 1991 Mar;37(1):15–26. doi: 10.1016/0165-0270(91)90017-t. [DOI] [PubMed] [Google Scholar]
  35. Singh A. K., Afink G. B., Venglarik C. J., Wang R. P., Bridges R. J. Colonic Cl channel blockade by three classes of compounds. Am J Physiol. 1991 Jul;261(1 Pt 1):C51–C63. doi: 10.1152/ajpcell.1991.261.1.C51. [DOI] [PubMed] [Google Scholar]
  36. Smirnov S. V., Aaronson P. I. Ca(2+)-activated and voltage-gated K+ currents in smooth muscle cells isolated from human mesenteric arteries. J Physiol. 1992 Nov;457:431–454. doi: 10.1113/jphysiol.1992.sp019386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Van Helden D. F. Spontaneous and noradrenaline-induced transient depolarizations in the smooth muscle of guinea-pig mesenteric vein. J Physiol. 1991 Jun;437:511–541. doi: 10.1113/jphysiol.1991.sp018609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Venglarik C. J., Singh A. K., Bridges R. J. Comparison of -nitro versus -amino 4,4'-substituents of disulfonic stilbenes as chloride channel blockers. Mol Cell Biochem. 1994 Nov 23;140(2):137–146. doi: 10.1007/BF00926752. [DOI] [PubMed] [Google Scholar]
  39. Wang Q., Hogg R. C., Large W. A. Properties of spontaneous inward currents recorded in smooth muscle cells isolated from the rabbit portal vein. J Physiol. 1992;451:525–537. doi: 10.1113/jphysiol.1992.sp019177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wang Q., Large W. A. Action of histamine on single smooth muscle cells dispersed from the rabbit pulmonary artery. J Physiol. 1993 Aug;468:125–139. doi: 10.1113/jphysiol.1993.sp019763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wangemann P., Wittner M., Di Stefano A., Englert H. C., Lang H. J., Schlatter E., Greger R. Cl(-)-channel blockers in the thick ascending limb of the loop of Henle. Structure activity relationship. Pflugers Arch. 1986;407 (Suppl 2):S128–S141. doi: 10.1007/BF00584942. [DOI] [PubMed] [Google Scholar]
  42. Wu G., Hamill O. P. NPPB block of Ca(++)-activated Cl- currents in Xenopus oocytes. Pflugers Arch. 1992 Feb;420(2):227–229. doi: 10.1007/BF00374996. [DOI] [PubMed] [Google Scholar]
  43. Zhang H., Bolton T. B. Effect of UK-84149 on voltage-activated calcium currents of single smooth muscle cells from guinea-pig and rabbit jejunum and rabbit coronary artery. Br J Pharmacol. 1995 Apr;114(8):1657–1665. doi: 10.1111/j.1476-5381.1995.tb14954.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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