دورية أكاديمية
أعرض في EDS

Subunit-specific inhibition of BK channels by piperine.

التفاصيل البيبلوغرافية
العنوان: Subunit-specific inhibition of BK channels by piperine.
المؤلفون: Kshatri A; Department of Basic Medical Sciences, Medical School, Universidad de La Laguna, Tenerife, Spain; Instituto de Tecnologias Biomedicas, Universidad de La Laguna, Tenerife, Spain., Rivero-Pérez B; Department of Basic Medical Sciences, Medical School, Universidad de La Laguna, Tenerife, Spain; Instituto de Tecnologias Biomedicas, Universidad de La Laguna, Tenerife, Spain., Giraldez T; Department of Basic Medical Sciences, Medical School, Universidad de La Laguna, Tenerife, Spain; Instituto de Tecnologias Biomedicas, Universidad de La Laguna, Tenerife, Spain. Electronic address: giraldez@ull.edu.es.
المصدر: Biophysical journal [Biophys J] 2024 Jul 16; Vol. 123 (14), pp. 1942-1953. Date of Electronic Publication: 2023 Sep 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0370626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1542-0086 (Electronic) Linking ISSN: 00063495 NLM ISO Abbreviation: Biophys J Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge, MA : Cell Press
Original Publication: New York, Published by Rockefeller University Press [etc.] for the Biophysical Society.
مواضيع طبية MeSH: Polyunsaturated Alkamides*/pharmacology , Benzodioxoles*/pharmacology , Piperidines*/pharmacology , Alkaloids*/pharmacology , Large-Conductance Calcium-Activated Potassium Channels*/metabolism , Large-Conductance Calcium-Activated Potassium Channels*/genetics , Protein Subunits*/metabolism, Humans ; HEK293 Cells ; Calcium/metabolism ; Potassium Channel Blockers/pharmacology
مستخلص: Piperine is the principal alkaloid present in black pepper and is well-known for its diverse pharmacological effects, including inhibition of different ion channels. Large conductance Ca 2+ -activated K + channels (BK) are widely expressed across several tissues and play a vital role in many physiological functions. In this study, we investigated the pharmacological effects of piperine on various BK channel subunit compositions (BKα, BKαβ 1,4 , BKαγ 1,3 ) expressed in HEK293T cells. Piperine in zero Ca 2+ reversibly inhibited currents from the pore-forming BKα channels in a dose-dependent manner with a half-maximal inhibitory concentration (IC 50 ) of 4.8 μM. Elevating the internal Ca 2+ concentration from 0 to 100 μM significantly attenuated the inhibitory effects of piperine on BKα channels. The mutation G311S in the pore domain failed to alter the modulatory effects of piperine, whereas deletion of the entire cytoplasmic domain from BKα channels ablated its inhibitory effects. Addition of either BKβ 1 or β 4 regulatory subunits did not alter the efficacy of piperine on BKα channels. Interestingly, co-expression of either BKγ 1 or BKγ 3 subunits greatly diminished the ability of piperine to inhibit BKα channels. Our findings demonstrate that piperine is a potent natural modulator of BKα/BKαβ 1,4 subunits but not BKαγ 1,3 subunits. The mechanism of piperine modulation appeared to be allosteric and differs from that of other BK pore blockers (paxilline, peptide toxins, and quaternary ammonium compounds). Together, our results unravel the potential of piperine to inhibit BK channels, providing a new tool to explore mechanisms underlying the effects of regulatory subunits.
Competing Interests: Declaration of interests The authors declare no competing interest.
(Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
References: Am J Physiol Regul Integr Comp Physiol. 2014 Sep 15;307(6):R571-84. (PMID: 24990859)
Phytother Res. 2021 Feb;35(2):680-700. (PMID: 32929825)
Int Rev Neurobiol. 2016;128:343-68. (PMID: 27238268)
Front Pharmacol. 2013 Nov 18;4:141. (PMID: 24302912)
J Cell Biol. 2014 Jul 21;206(2):151-62. (PMID: 25049269)
Biochemistry. 1994 May 17;33(19):5819-28. (PMID: 7514038)
J Biol Chem. 2000 Mar 3;275(9):6453-61. (PMID: 10692449)
Int Rev Neurobiol. 2016;128:439-75. (PMID: 27238271)
Pflugers Arch. 1981 Aug;391(2):85-100. (PMID: 6270629)
J Gen Physiol. 2005 Oct;126(4):393-412. (PMID: 16186565)
Channels (Austin). 2017 Jan 2;11(1):66-78. (PMID: 27440457)
Recept Channels. 1995;3(3):185-99. (PMID: 8821792)
Nature. 2017 Jan 5;541(7635):46-51. (PMID: 27974795)
Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2194-2200. (PMID: 31932443)
Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2064-9. (PMID: 25653338)
J Gen Physiol. 2020 Jun 1;152(6):. (PMID: 32275741)
Toxicon. 2011 Apr;57(5):686-94. (PMID: 21300077)
Pflugers Arch. 2003 May;446(2):248-55. (PMID: 12739163)
Oncogene. 2007 Apr 12;26(17):2525-34. (PMID: 17146446)
Pflugers Arch. 2018 Sep;470(9):1271-1289. (PMID: 29748711)
J Gen Physiol. 2017 Apr 3;149(4):431-441. (PMID: 28246116)
Mol Pharmacol. 2012 Jan;81(1):21-30. (PMID: 21984254)
Annu Rev Physiol. 2019 Feb 10;81:113-137. (PMID: 30742788)
Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16657-62. (PMID: 24067659)
Biochem Pharmacol. 2013 Jun 15;85(12):1827-36. (PMID: 23623790)
Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8999-9011. (PMID: 30575945)
Nature. 2017 Jan 5;541(7635):52-57. (PMID: 27974801)
Nucleic Acids Res. 2016 Jul 08;44(W1):W267-71. (PMID: 27166368)
Nature. 2010 Jul 22;466(7305):513-6. (PMID: 20613726)
PLoS One. 2012;7(8):e41664. (PMID: 22899999)
J Pharmacol Exp Ther. 2008 Dec;327(3):657-64. (PMID: 18801945)
Front Mol Neurosci. 2018 Jul 30;11:258. (PMID: 30104956)
Kidney Int. 2010 Nov;78(10):956-62. (PMID: 20720523)
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5562-7. (PMID: 10792058)
Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14512-14521. (PMID: 32513714)
FEBS Lett. 2000 May 26;474(1):99-106. (PMID: 10828459)
Nat Commun. 2022 Nov 9;13(1):6784. (PMID: 36351900)
J Neurosci Res. 2004 Oct 15;78(2):224-34. (PMID: 15378515)
J Biol Chem. 2014 Jul 4;289(27):18860-72. (PMID: 24778177)
Br J Pharmacol. 2005 Mar;144(6):781-90. (PMID: 15685214)
Nat Protoc. 2013 Nov;8(11):2281-2308. (PMID: 24157548)
J Gen Physiol. 2019 Oct 7;151(10):1173-1189. (PMID: 31427379)
Channels (Austin). 2015;9(5):317-23. (PMID: 26542628)
Proc Natl Acad Sci U S A. 2020 Jan 14;117(2):1021-1026. (PMID: 31879339)
J Pharmacol Exp Ther. 2012 Aug;342(2):453-60. (PMID: 22580348)
J Gen Physiol. 2010 May;135(5):481-94. (PMID: 20421373)
FEBS Lett. 2001 Sep 21;505(3):369-73. (PMID: 11576530)
Nat Rev Drug Discov. 2021 Mar;20(3):200-216. (PMID: 33510482)
J Biol Chem. 2012 Jun 8;287(24):20509-21. (PMID: 22474334)
المشرفين على المادة: 0 (Polyunsaturated Alkamides)
U71XL721QK (piperine)
0 (Benzodioxoles)
0 (Piperidines)
0 (Alkaloids)
0 (Large-Conductance Calcium-Activated Potassium Channels)
0 (Protein Subunits)
SY7Q814VUP (Calcium)
0 (Potassium Channel Blockers)
تواريخ الأحداث: Date Created: 20230913 Date Completed: 20240717 Latest Revision: 20240811
رمز التحديث: 20240812
مُعرف محوري في PubMed: PMC11309970
DOI: 10.1016/j.bpj.2023.09.002
PMID: 37700524
قاعدة البيانات: MEDLINE
الوصف
تدمد:1542-0086
DOI:10.1016/j.bpj.2023.09.002