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NO‐dependent vasodilation is coupled to coordinated activation of connexin‐ and pannexin‐based hemichannels in endothelial cells
Author(s) -
Lillo Mauricio,
Gaete Pablo,
Saez Juan Carlos,
Figueroa Xavier
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.853.8
Subject(s) - chemistry , pannexin , connexin , probenecid , vasodilation , nitric oxide , soluble guanylyl cyclase , acetylcholine , carbenoxolone , pharmacology , lucifer yellow , intracellular , gap junction , microbiology and biotechnology , guanylate cyclase , biophysics , biochemistry , endocrinology , biology , organic chemistry
Nitric oxide(NO)activates connexin(Cx)‐based channels by S‐nitrosylation, but its effect on pannexin(Panx)channels has not been determined. We evaluated the involment of Cx‐and Panx‐based hemichannels in the endothelium‐mediated NO‐dependent vasodilation induced by acetylcholine (ACh) in rat arterial mesenteric bed of rat. Hemichannel activity was assessed by ethidium (Etd) or Lucifer Yellow(LY)uptake. Vessels did not show Etd uptake in control conditions. ACh stimulation induced a strong increase in Etd and LY uptake that was blocked by the Panx blockers probenecid and Panx10, and also carbenoxolone, but only attenuated by La 3+ (Cx hemichannels blocker) and 18‐beta‐glycyrrhetinic acid. In addition, Etd uptake was also blocked by the inhibition of NO synthase with NG‐nitro‐L‐arginine (L‐NA), guanylate cyclase soluble with ODQ and PKG with KT5823. The same results were observed with the NO donor S‐nitroso‐N‐acetyl‐ D‐penicillamine (SNAP). However, the increase in Etd uptake activated by the analogue of cGMP, 8‐Br‐cGMP, was only sensitive to probenecid and KT5823, but not to La 3+ . Interestingly, probenecid potentiated the NO‐dependent, ACh‐induced vasodilation. These results indicate that Cx‐based hemichannels are activated directly by NO, whereas the cGMP/PKG pathway induced the opening of Panx‐formed hemichannels. FONDECYT 1100850, 1090757, 1111033, Anillos ACT‐71