Inhibition of depolarization-induced [H-3]noradrenaline release from SH-SY5Y human neuroblastoma cells by some second-generation H-1 receptor antagonists through blockade of store-operated Ca2+ channels (SOCs)

Citation
M. Taglialatela et al., Inhibition of depolarization-induced [H-3]noradrenaline release from SH-SY5Y human neuroblastoma cells by some second-generation H-1 receptor antagonists through blockade of store-operated Ca2+ channels (SOCs), BIOCH PHARM, 62(9), 2001, pp. 1229-1238
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
9
Year of publication
2001
Pages
1229 - 1238
Database
ISI
SICI code
0006-2952(20011101)62:9<1229:IOD[RF>2.0.ZU;2-U
Abstract
In the present study, the effect of the blockade of membrane calcium channe ls activated by intracellular Ca2+ store depletion on basal and depolarizat ion-induced [H-3]norepinephrine ([H-3]NE) release from SH-SY5Y human neurob lastoma cells was examined. The second-generation H-1 receptor blockers ast emizole, terfenadine, and loratadine, as well as the first-generation compo und hydroxyzine, inhibited [H-3]NE release induced by high extracellular K concentration ([K+](e)) depolarization in a concentration-dependent manner (the IC(50)s were 2.3, 1.7, 4.8, and 9.4 muM, respectively). In contrast, the more hydrophilic second-generation H-1 receptor blocker cetirizine was completely ineffective (0.1-30 muM). The inhibition of high [K+](e)-induced [H-3]NE release by H-1 receptor blockers seems to be related to their abil ity to inhibit Ca2+ channels activated by Ca-i(2+) store depletion (SOCs). In fact, astemizole, terfenadine, loratadine, and hydroxyzine, but not ceti rizine, displayed a dose-dependent inhibitory action on the increase in int racellular Ca2+ concentrations ([Ca2+](i)) obtained with extracellular Ca2 reintroduction after Ca-i(2+) store depletion with thapsigargin (1 muM), a n inhibitor of the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA ) pump. The rank order of potency for SOC inhibition by these compounds clo sely correlated with their inhibitory properties on depolarization-induced [H-3]NE release from SH-SY5Y human neuroblastoma cells. Nimodipine (1 muM) plus omega -conotoxin (100 nM) did not interfere with the present model for SOC activation. In addition, the inhibition of depolarization-induced [H-3 ]NE release does not seem to be attributable to the blockade of the K+ curr ents carried by the K+ channels encoded by the human Ether-a-Gogo Related G ene (I-HERG) by these antihistamines. In fact, whole-cell voltage-clamp exp eriments revealed that the IC50 for astemizole-induced hERG blockade is abo ut 300-fold lower than that for the inhibition of high K+-induced [H-3]NE r elease. Furthermore, current-clamp experiments in SH-SY5Y cells showed that concentrations of astemizole (3 muM) which were effective in preventing de polarization-induced [H-3]NE release were unable to interfere with the cell membrane potential under depolarizing conditions (100 mM [K+](e)), suggest ing that hERG K+ channels do not contribute to membrane potential control d uring exposure to elevated [K+](e). Collectively, the results of the presen t study suggest that, in SH-SY5Y human neuroblastoma cells, the inhibition of SOCs by some second-generation antihistamines can prevent depolarization -induced neurotransmitter release. (C) 2001 Elsevier Science Inc. All right s reserved.