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Patton WF, Wang Q, Chiang ET, et al. Antamanide Prevents Bradykinin-lnduced Filamin Translocation by Inhibiting Extracellular Calcium Influx. Drug Deliv. 1997;4(4):247-54doi: 10.3109/10717549709052010.
Patton, W. F., Wang, Q., Chiang, E. T., Hechtman, H. B., & Shepro, D. (1997). Antamanide Prevents Bradykinin-lnduced Filamin Translocation by Inhibiting Extracellular Calcium Influx. Drug delivery, 4(4), 247-54. https://doi.org/10.3109/10717549709052010
Patton, W F, et al. "Antamanide Prevents Bradykinin-lnduced Filamin Translocation by Inhibiting Extracellular Calcium Influx." Drug delivery vol. 4,4 (1997): 247-54. doi: https://doi.org/10.3109/10717549709052010
Patton WF, Wang Q, Chiang ET, Hechtman HB, Shepro D. Antamanide Prevents Bradykinin-lnduced Filamin Translocation by Inhibiting Extracellular Calcium Influx. Drug Deliv. 1997;4(4):247-54. doi: 10.3109/10717549709052010. PMID: 26582443.
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Drug Deliv. 1997;4(4):247-54. doi: 10.3109/10717549709052010.

Antamanide Prevents Bradykinin-lnduced Filamin Translocation by Inhibiting Extracellular Calcium Influx.

Drug delivery

W F Patton, Q Wang, E T Chiang, H B Hechtman, D Shepro

Affiliations

  1. a Microvascular Research Laboratory, Biological Science Center, Boston University, Boston, Massachusetts, USA.
  2. b Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 26582443 DOI: 10.3109/10717549709052010

Abstract

Bradykinin-induced paracellular gap formation in cultured endothelial cells (ECs) is preceded by cytoskeletal rearrangement. Actin binding proteins, such as nonmuscle filamin, perform a pivotal role in modulating actin organization. In response to bradykinin treatment, EC filamin translocates from the cell periphery to the cytosol within 1 min and the dynamics of filamin translocation parallel intracellular Ca(2+) increases. Intracellular Ca(2+) increases are essential for bradykinin-induced filamin translocation. In this study, we examine the role of extracellular Ca(2+) influx in mediating bradykinin-induced filamin translocation. Several K(+) channel blockers, including antamanide, tetraethylam-monium chloride (TEA), and charybdotoxin (CTX), are evaluated. All of these agents inhibit extracellular Ca(2+) influx with minimal or partial inhibition of intracellular Ca(2+) release. Bradykinin-induced filamin translocation is prevented by pretreatment with these K(+) channel blockers. Moreover, incubation of ECs in high-K(+) saline inhibits bradykinin-induced extracellular Ca(2+) influx as well as filamin translocation. To examine the efficacy of antamanide as an anti-inflammatory drug that affects filamin translocation, bradykinin-induced paracellular gap formation is quantified and compared in the presence or absence of antamanide pretreatment. Antamanide does not completely block bradykinin-induced gap formation; however, a significant attenuation is observed. This suggests that extracellular Ca(2+) influx is required for bradykinin-induced filamin translocation, which in part regulates microvascular EC barrier function, and that antamanide may be a useful anti-inflammatory agent.

Keywords: Antamanide; Bradykinin; Endothelium; Extracellular Ca2+ Influx; Filamin; Permeability

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