Current perspectives in the pharmacological studies of store-operated Ca2+entry blockers

The store-operated Ca2+ entry (SOCE) pathway has aroused much interest rece ntly not only because of its unusual nature as retrograde signaling, but al so due to its wide occurrence and its possible role in physiological and pa thophysiological situations. A number of synthetic or naturally occurring d rugs recently used to block this Ca2+ entry pathway are briefly reviewed. A lthough 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 usin g them as putative tools to study SOCE. For instance, the highly variable p otency of some synthetic blockers (SK&F 96365 and LOE 908) to inhibit SOCE has provided indirect evidence for the heterogeneous nature of the SOCE cha nnels, an observation consistent with the differential Mn2+ permeability th rough SOCE in various cell types. The use of SK&F 96365 at relatively high concentrations has unexpectedly revealed its potential as an opener of a no vel cation entry pathway. The ability of LU52396 to discriminate the SOCE c hannel in its closed/open states may be useful in the analysis of the kinet ics of SOCE channel activation/inactivation. The possible presence of both agonistic and antagonistic saponins derived from ginseng plants for the stu dy of SOCE deserves more rigorous experimental investigations, which may la y new ground for the development of new types of Ca2+ antagonists (and/or a gonists) from the natural resources.