We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Lysophosphatidic acid-LPA<sub>1</sub> receptor–Rho–Rho kinase-induced up-regulation of Na<sub>v</sub>1.7 sodium channel mRNA and protein in adrenal chromaffin cells: enhancement of <sup>22</sup>Na<sup>+</sup> influx, <sup>45</sup>Ca<sup>2+</sup> influx and catecholamine secretion
- Authors
Maruta, Toyoaki; Yanagita, Toshihiko; Matsuo, Kiyotaka; Uezono, Yasuhito; Satoh, Shinya; Nemoto, Takayuki; Yoshikawa, Norie; Kobayashi, Hideyuki; Takasaki, Mayumi; Wada, Akihiko
- Abstract
In cultured bovine adrenal chromaffin cells, chronic (≥ 24 h) treatment with lysophosphatidic acid (LPA) augmented veratridine-induced 22Na+ influx via Nav1.7 by ∼22% (EC50 = 1 nmol/L), without changing nicotine-induced 22Na+ influx via nicotinic receptor-associated channel. LPA enhanced veratridine (but not nicotine)-induced 45Ca2+ influx via voltage-dependent calcium channel and catecholamine secretion. LPA shifted concentration–response curve of veratridine for 22Na+ influx upward, without altering the EC50 of veratridine. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced 22Na+ influx by twofold in non-treated and LPA-treated cells. Whole-cell patch-clamp analysis showed that peak Na+ current amplitude was greater by 39% in LPA (100 nmol/L for 36 h)-treated cells; however, I–V curve and steady-state inactivation/activation curves were comparable between non-treated and LPA-treated cells. LPA treatment (≥ 24 h) increased cell surface [3H]saxitoxin binding by ∼28%, without altering the Kd value; the increase was prevented by cycloheximide, actinomycin D, or Ki16425, dioctylglycerol pyrophosphate 8:0 (two inhibitors of LPA1 and LPA3 receptors), or botulinum toxin C3 (Rho inhibitor), Y27632 (Rho kinase inhibitor), consistent with LPA1 receptor expression in adrenal chromaffin cells. LPA raised Nav1.7 mRNA level by ∼37%. Thus, LPA–LPA1 receptor–Rho/Rho kinase pathway up-regulated cell surface Nav1.7 and Nav1.7 mRNA levels, enhancing veratridine-induced Ca2+ influx and catecholamine secretion.
- Subjects
LYSOPHOSPHOLIPIDS; MESSENGER RNA; CHROMAFFIN cells; CALCIUM channels; CATECHOLAMINES
- Publication
Journal of Neurochemistry, 2008, Vol 105, Issue 2, p401
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.05143.x