IngentaConnect Novel Effects of Minocycline on Ca2+-Dependent Cl Secretion in Hu...

Abstract:

The present study concerns previously unreported effects of the antibiotic minocycline on the transepithelial Cl^- transport in Calu-3 cells, which display electrophysiological properties consistent with human airway serous cells. Basolateral 4,4 prime -diisothiocyanatostilbene-2,2 prime -disulfonic acid (DIDS, 200 M) augmented Cl^- secretion, which was detected as a 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, 100 M, a Cl^- channel blocker)-sensitive short-circuit current (I_sc). The DIDS-induced I_sc was composed of Ca²⁺-activated K⁺ (K_Ca) channel-dependent and -independent components. The former was selectively inhibited by 1,2-bis(o-aminophenoxy)ethane-N,N,N,N-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA/AM, 10 M), charybdotoxin (ChTx, 100 nM), clotrimazole (10 M), basolateral Ca²⁺ removal, and basolateral minocycline (IC₅₀ = 20 M). The latter was attenuated by basolateral BaCl (5 mM). In contrast, forskolin (10 M)-induced I_sc, which is insensitive to BAPTA/AM and ChTx, was unaffected by minocycline (100 M). ATP-induced I_sc was partially inhibited by basolateral but not by apical minocycline. I_sc due to basolateral application of ionomycin (1 M) was markedly suppressed by NPPB and basolateral Ca²⁺ removal. These inhibitory effects were mimicked by minocycline applied only from the basolateral side of the monolayer. In the basolateral absence of Ca²⁺, 1-ethyl-2-benzimdazolinone (500 M), a K_Ca channel opener, generated a sustained I_sc sensitive to ChTx. Minocycline had no significant effect on the ChTx-sensitive component of the I_sc. It is concluded that minocycline inhibits K_Ca channel-dependent Cl^- secretion via a blockade of Ca²⁺ influx across the basolateral membrane from the extracellular side. Copyright 2001 Academic Press.

Keywords: Ca²⁺-activated K⁺ channels; Ca²⁺ influx; Cl^- secretion; minocycline; short-circuit current

Language: English

Document Type: Research article

Affiliations: School of Medicine, Nagoya University, Showa-ku, Nagoya, 466-8550, Japan:

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Novel Effects of Minocycline on Ca2+-Dependent Cl- Secretion in Human Airway Epithelial Calu-3 Cells

Novel Effects of Minocycline on Ca²⁺-Dependent Cl^- Secretion in Human Airway Epithelial Calu-3 Cells