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Further studies on the interaction of loperamide with capacitative calcium entry in Leukemic HL‐60 cells
Author(s) -
Daly John W.,
CameriniOtero Carol,
Shapiro Craig A.,
Ma Jingyuan,
Ziffer Herman,
Vélez Leykza,
Harper Jacquie L.
Publication year - 2006
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20150
Subject(s) - loperamide , calcium , chemistry , calcium in biology , pharmacology , endocrinology , thapsigargin , medicine , diarrhea
Loperamide at 3–10 µM has augmentative effects on calcium levels elevated by capacitative calcium entry (CCE) in leukemic HL‐60 cells after release of intracellular calcium by ATP or thapsigargin (Harper et al. [1997] Proc Natl Acad Sci USA 94:14912–14917). The effect of loperamide on calcium levels was absent at a pH value of 6.8, a pH at which CCE is not active in HL‐60 cells. Further investigations of HL‐60 cells in recent years revealed a great reduction in the magnitude of the loperamide response. However, when preceded by a CCE blocker, namely N‐methylnitrendipine (MRS 1844) or N‐propargylnitrendipine (MRS 1845), loperamide caused a significant reversal of the blockade. Six structural analogs of loperamide were synthesized, but only two showed loperamide‐like activity. Drug Dev. Res. 67:842–851, 2006. Published 2007 Wiley‐Liss, Inc.