20-HETE inotropic effects involve the activation of a nonselective cationic current in airway smooth muscle.
20-Hydroxyeicosatetraenoic acid (20-HETE) controls several mechanisms such as vasoactivity, mitogenicity, and ion transport in various tissues. Our goal was to quantify the effects of 20-HETE on the electrophysiological properties of airway smooth muscle (ASM). Isometric tension measurements, performed on guinea pig ASM, showed that 20-HETE induced a dose-dependent inotropic effect with an EC50 value of 1.5 microM. This inotropic response was insensitive to GF-109203X, a PKC inhibitor. The sustained contraction, requiring Ca2+ entry, was partially blocked by either 100 microM Gd3+ or 1 microM nifedipine, revealing the involvement of noncapacitative Ca2+ entry and L-type Ca2+ channels, respectively. Microelectrode measurements showed that 3 microM 20-HETE depolarized the membrane potential in guinea pig ASM by 13 +/- 2mV(n = 7), as did 30 microM 1-oleoyl-2-acetyl-sn-glycerol. Depolarizing effects were also observed in the absence of epithelium. Patch-clamp recordings demonstrated that 1 microM 20-HETE activated a nonselective cationic inward current that may be supported by the activation of transient receptor potential channels. The presence of canonical transient receptor potential mRNA was confirmed by RT-PCR in guinea pig ASM cells.
Cloutier
Martin
M
Le Bilarium, Faculty of Medicine, Dept. of Physiology and Biophysics, Univ. of Sherbrooke, 3001 12th Ave. N., Sherbrooke, Quebec, Canada J1H 5N4.
Campbell
Shirley
S
Basora
Nuria
N
Proteau
Sonia
S
Payet
Marcel D
MD
Rousseau
Eric
E
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects* / Q000502:physiology*
D002412:Cations; D004075:Diglycerides; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007211:Indoles; D008301:Maleimides; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D002118:Calcium