Home LiteratureArticle Details
PMID: 7516040 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The isoquinoline derivative LOE 908 selectively blocks vasopressin-activated nonselective cation currents in A7r5 aortic smooth muscle cells.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 349 ·No. 3 ·1994-03-00 ·Pages 301-7

Krautwurst D, Degtiar VE, Schultz G, Hescheler J

Abstract

The effect of (R,S)-(3,4-dihydro 6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl- N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908), a cation channel blocker in HL-60 promyeloblasts, was studied in the A7r5 smooth muscle cell line from rat thoracic aorta, using the whole-cell patch-clamp technique. At a holding potential of -60 mV, application of vasopressin induced a nonselective cation conductance in voltage-clamped A7r5 cells. The current-voltage relation was linear, and currents reversed close to 0 mV regardless of the chloride gradient. The activation of the nonselective cation conductance by vasopressin was not affected by dialysing cells with Ca(2+)-free internal solution. LOE 908 blocked this current in a concentration-dependent manner with an IC50 of 560 nM, whereas dihydropyridine-sensitive Ba2+ current through voltage-dependent Ca2+ channels was blocked with an IC50 of 28 microM. Another organic blocker of receptor-mediated Ca2+ entry, 1-beta-[3-(4-methoxyphenyl)-propoxy]-4-methoxyphenethyl-1H-imidazole hydrochloride (SK&F 96365), blocked both, the vasopressin-induced nonselective conductance and the voltage-activated Ba2+ current with similar IC50 values of 13 microM and 8 microM, respectively. The rank order of potency of inorganic blockers on the vasopressin-induced inward current was Gd3+ > La3+ > Cd2+. Vasopressin-induced non-selective cation current was also observed in pertussis toxin-pretreated A7r5 cells but was completely abolished after infusion of the GDP analogue, guanosine 5'-O-[3-thio]diphosphate, from the patch pipette. Furthermore, vasopressin induced a transient outward current, suggesting a Ca(2+)-activated K(+)-current, which overlapped with the nonselective cation conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms
Acetamides/pharmacology Animals Aorta, Thoracic/drug effects Calcium/metabolism Cells, Cultured Electrophysiology GTP-Binding Proteins/drug effects Imidazoles/pharmacology Ion Channels/drug effects Isoquinolines/pharmacology Muscle, Smooth, Vascular/cytology,drug effects Rats Vasopressins/pharmacology
Chemicals
Acetamides Imidazoles Ion Channels Isoquinolines Vasopressins LOE 908 GTP-Binding Proteins 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Krautwurst D
Institut für Pharmakologie, Freie Universität Berlin, Germany.
Degtiar V E
Schultz G
Hescheler J
References (46)
46 references, click to expand
  1. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
    Pflugers Arch. 1981 Aug;391(2):85-100 PMID: 6270629
  2. Receptor-operated calcium-permeable channels in vascular smooth muscle.
    J Cardiovasc Pharmacol. 1989;14 Suppl 6:S49-58 PMID: 2478825
  3. Effect of external Cd2+ and other divalent cations on carbachol-activated non-selective cation channels in guinea-pig ileum.
    J Physiol. 1991 Oct;442:447-63 PMID: 1724672
  4. Aluminum: a requirement for activation of the regulatory component of adenylate cyclase by fluoride.
    Proc Natl Acad Sci U S A. 1982 Aug;79(16):4888-91 PMID: 6289322
  5. Role of Ca2(+)-ATPases in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2(+)-ATPase inhibitor, thapsigargin.
    Agents Actions. 1990 Jan;29(1-2):8-15 PMID: 2139301
  6. Ca2+ influx following receptor activation.
    Trends Pharmacol Sci. 1991 Aug;12(8):289-92 PMID: 1658997
  7. Cellular mechanisms regulating [Ca2+]i smooth muscle.
    Annu Rev Physiol. 1989;51:315-29 PMID: 2653185
  8. Characterization of two putative smooth muscle cell lines from rat thoracic aorta.
    Exp Cell Res. 1976 Mar 15;98(2):349-66 PMID: 943301
  9. Cell calcium and its regulation in smooth muscle.
    FASEB J. 1989 Sep;3(11):2266-76 PMID: 2506092
  10. 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 PMID: 686171
  11. Acetylcholine activates nonselective cation channels in guinea pig ileum through a G protein.
    Am J Physiol. 1990 Jun;258(6 Pt 1):C1173-8 PMID: 1694399
  12. Muscarinic activation of ionic currents measured by a new whole-cell recording method.
    J Gen Physiol. 1988 Aug;92(2):145-59 PMID: 2459299
  13. G protein control of inositol lipids in intact vascular smooth muscle.
    FEBS Lett. 1990 Jul 30;268(1):91-4 PMID: 2166688
  14. G-proteins are involved in contractile responses of isolated mesenteric resistance arteries to agonists.
    Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):462-8 PMID: 2123967
  15. Regulation of calcium influx by second messengers in rat mast cells.
    Nature. 1988 Aug 11;334(6182):499-504 PMID: 2457169
  16. A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle.
    Nature. 1987 Jul 16-22;328(6127):275-8 PMID: 2439921
  17. Novel potent inhibitor of receptor-activated nonselective cation currents in HL-60 cells.
    Mol Pharmacol. 1993 May;43(5):655-9 PMID: 7684814
  18. Lateral mobility of the phospholipase C-activating vasopressin V1-type receptor in A7r5 smooth muscle cells: a comparison with the adenylate cyclase-coupled V2-receptor.
    EMBO J. 1990 Sep;9(9):2693-9 PMID: 2143982
  19. Large conductance calcium-activated non-selective cation channel in smooth muscle cells isolated from rat portal vein.
    J Physiol. 1991 Jun;437:461-75 PMID: 1716314
  20. Endogenous and exogenous agonist-induced changes in the coupling between [Ca2+]i and force in rat resistance arteries.
    Pflugers Arch. 1992 Apr;420(5-6):536-43 PMID: 1614828
  21. Dihydropyridine sensitive calcium channels in a smooth muscle cell line.
    Biochem Biophys Res Commun. 1985 Feb 28;127(1):71-9 PMID: 2579654
  22. Receptor-mediated Ca2+ entry: diversity of function and mechanism.
    Trends Pharmacol Sci. 1989 Jan;10(1):8-10 PMID: 2556820
  23. Evidence for receptor-mediated bivalent-cation entry in A10 vascular smooth-muscle cells.
    Biochem J. 1990 Apr 1;267(1):277-80 PMID: 2158310
  24. Noradrenaline contracts arteries by activating voltage-dependent calcium channels.
    Nature. 1988 Nov 24;336(6197):382-5 PMID: 2848201
  25. Thapsigargin stimulates Ca2+ entry in vascular smooth muscle cells: nicardipine-sensitive and -insensitive pathways.
    Am J Physiol. 1992 May;262(5 Pt 1):C1258-65 PMID: 1534201
  26. Mechanisms of action of transmitters and other substances on smooth muscle.
    Physiol Rev. 1979 Jul;59(3):606-718 PMID: 37533
  27. Regulation of phospholipase C by G proteins.
    Trends Biochem Sci. 1992 Dec;17(12):502-6 PMID: 1335185
  28. Signal transduction of V1-vascular vasopressin receptors.
    Regul Pept. 1992 Mar 5;38(1):1-11 PMID: 1533467
  29. Noradrenaline-evoked cation conductance recorded with the nystatin whole-cell method in rabbit portal vein cells.
    J Physiol. 1991 Apr;435:21-39 PMID: 1770436
  30. Multiple signaling pathways of V1-vascular vasopressin receptors of A7r5 cells.
    Endocrinology. 1991 Dec;129(6):2845-56 PMID: 1659517
  31. G proteins: transducers of receptor-generated signals.
    Annu Rev Biochem. 1987;56:615-49 PMID: 3113327
  32. Ca2+ influx stimulated by vasopressin is mediated by phosphoinositide hydrolysis in rat smooth muscle cells.
    Biochem Biophys Res Commun. 1989 Jun 15;161(2):677-82 PMID: 2544169
  33. SK&F 96365, a novel inhibitor of receptor-mediated calcium entry.
    Biochem J. 1990 Oct 15;271(2):515-22 PMID: 2173565
  34. Potassium, chloride and non-selective cation conductances opened by noradrenaline in rabbit ear artery cells.
    J Physiol. 1990 Apr;423:551-68 PMID: 1696988
  35. Agonist-induced activation of rat mesenteric resistance vessels: comparison between noradrenaline and vasopressin.
    J Cardiovasc Pharmacol. 1988;12 Suppl 5:S128-33 PMID: 2469870
  36. Thapsigargin discharges intracellular calcium stores and induces transmembrane currents in human endothelial cells.
    Pflugers Arch. 1993 Mar;422(6):552-7 PMID: 8469608
  37. Role of G proteins in calcium channel modulation.
    Annu Rev Physiol. 1990;52:275-92 PMID: 1691905
  38. Calcium currents in the A7r5 smooth muscle-derived cell line. An allosteric model for calcium channel activation and dihydropyridine agonist action.
    J Gen Physiol. 1992 Mar;99(3):367-90 PMID: 1316936
  39. Differential blockade of agonist- and depolarization-induced 45Ca2+ influx in smooth muscle cells.
    Am J Physiol. 1989 Oct;257(4 Pt 1):C607-11 PMID: 2679123
  40. Modulation of electrical activity and of intracellular calcium oscillations of smooth muscle cells by calcium antagonists, agonists, and vasopressin.
    J Cardiovasc Pharmacol. 1991;18 Suppl 10:S7-14 PMID: 1725008
  41. Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production.
    Biochem J. 1992 Dec 15;288 ( Pt 3):1025-35 PMID: 1281979
  42. Vasopressin modulates the spontaneous electrical activity in aortic cells (line A7r5) by acting on three different types of ionic channels.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):9365-9 PMID: 2461570
  43. Relationship between force and Ca2+ concentration in smooth muscle as revealed by measurements on single cells.
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):4109-13 PMID: 3131775
  44. Changes in cytosolic calcium level in vascular smooth muscle strip measured simultaneously with contraction using fluorescent calcium indicator fura 2.
    J Pharmacol Exp Ther. 1988 Jul;246(1):294-300 PMID: 2455792
  45. A small-conductance charybdotoxin-sensitive, apamin-resistant Ca(2+)-activated K+ channel in aortic smooth muscle cells (A7r5 line and primary culture).
    Pflugers Arch. 1992 Apr;420(5-6):417-23 PMID: 1377376
  46. Agonist-dependent Ca2+ and Mn2+ entry dependent on state of filling of Ca2+ stores in aortic smooth muscle cells of the rat.
    J Physiol. 1990 Aug;427:171-86 PMID: 2213595
Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00169297
Published
1994-03-00
Pages
301-7
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00169297 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2