title: Effects of chloride channel blockers on hypotonicity-induced contractions of the rat trachea.
abstract: 1. We have investigated the inhibitory effects of blockers of volume-activated (Cl(vol)) and calcium-activated (Cl(Ca)) chloride channels on hypotonic solution (HS)-induced contractions of rat trachea, comparing their effects with those of the voltage-dependent calcium channel (VDCC) blocker nifedpine. 2. HS elicited large, stable contractions that were partially dependent on the cellular chloride gradient; a reduction to 41.45+/-7.71% of the control response was obtained when extracellular chloride was removed. In addition, HS-induced responses were reduced to 26.8+/-5.6% of the control by 1 microm nifedipine, and abolished under calcium-free conditions, indicating a substantial requirement for extracellular calcium entry, principally via VDCCs. 3. The established Cl(vol) blockers tamoxifen (</=10 microm) and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (1-100 microm), at concentrations previously reported to inhibit Cl(vol) in smooth muscle, did not significantly inhibit HS-induced contractions. 4. In contrast, the recognized Cl(Ca) blocker niflumic acid (NFA; 1-100 microm) produced a reversible, concentration-dependent inhibition of HS responses, with a reduction to 36.6+/-6.4% of control contractions at the highest concentration. The mixed Cl(vol) and Cl(Ca) blocker, 5-nitro 2-(3-phenylpropylamine) benzoic acid (NPPB; 10-100 microm) also elicited concentration-related inhibition of HS-induced contractions, producing a decrease to 35.9+/-11.3% of the control at 100 microm. 5. Our results show that HS induces reversible, chloride-dependent contractions of rat isolated trachea that were inhibited by NFA and NPPB, while exhibiting little sensitivity to recognized blockers of Cl(vol). The data support the possibility that opening of calcium-activated chloride channels under hypotonic conditions in respiratory smooth muscle may ultimately lead to VDCC-mediated calcium entry and contraction.
authors.affiliation: Laboratório de Farmacologia dos Canais Iônicos - LAFACI, Departamento de Ciências Fisiológicas, CCS, Universidade Estadual do Ceará, Av. Paranjana 1700, Fortaleza CE 60740-000, Brazil.
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Coelho
authors.forename: Emmanuel P
authors.initials: EP
authors.lastname: Souza
authors.forename: Pedro M G
authors.initials: PM
authors.lastname: Soares
authors.forename: Ana Vaneska P
authors.initials: AV
authors.lastname: Meireles
authors.forename: Geam C M
authors.initials: GC
authors.lastname: Santos
authors.forename: Henrique C
authors.initials: HC
authors.lastname: Scarparo
authors.forename: Ana Maria S
authors.initials: AM
authors.lastname: Assreuy
authors.forename: David N
authors.initials: DN
authors.lastname: Criddle
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007038:Hypotonic Solutions / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D018118:Chloride Channels; D007038:Hypotonic Solutions; D013629:Tamoxifen; D009544:Niflumic Acid; D009543:Nifedipine