Jpn. J. Pharmacol. 81 (3), 253 - 258 (1999)

-Current Perspective-
Current Perspectives in the Pharmacological Studies
of Store-Operated Ca2+ Entry Blockers

Yuk Man Leung and Chiu Yin Kwan*

Department of Medicine, Faculty of Health Sciences, McMaster University,
1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5
(*) To whom correspondence should be addressed; CYK is supported by a Career Investigator Award by the Heart and Stroke Foundation of Ontario, Canada.

Abstract: The store-operated Ca2+ entry (SOCE) pathway has aroused much interest recently not only because of its unusual nature as retrograde signaling, but also due to its wide occurrence and its possible role in physiological and pathophysiological situations. A number of synthetic or naturally occurring drugs recently used to block this Ca2+ entry pathway are briefly reviewed. Although important and interesting information has been obtained using these putative SOCE blockers described in this review, they indeed have sites of action other than the SOCE channels, and caution must be exercised in using them as putative tools to study SOCE. For instance, the highly variable potency of some synthetic blockers (SKandF 96365 and LOE 908) to inhibit SOCE has provided indirect evidence for the heterogeneous nature of the SOCE channels, an observation consistent with the differential Mn2+ permeability through SOCE in various cell types. The use of SKandF 96365 at relatively high concentrations has unexpectedly revealed its potential as an opener of a novel cation entry pathway. The ability of LU52396 to discriminate the SOCE channel in its closed/open states may be useful in the analysis of the kinetics of SOCE channel activation/inactivation. The possible presence of both agonistic and antagonistic saponins derived from ginseng plants for the study of SOCE deserves more rigorous experimental investigations, which may lay new ground for the development of new types of Ca2+ antagonists (and/or agonists) from the natural resources.

Keywords: Calcium channel, Tetrandrine, Ginsenoside, SKandF 76365, LOE 908, LU52396

Copyrightę The Japanese Pharmacological Society 1999

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