Capacitative Ca²⁺ entry in HL-60 cells: tetrandrine and SK & F 96365 as probes.

Agonist-activated Ca²⁺ entry is important in many biological responses such as secretion and cell growth(1,2). In nonexcitable cells which have no voltage-operated Ca²⁺ channels (VOCC), agonist-receptor interaction can trigger Ca²⁺ entry across the plasmalemma via several entry pathways(1-3) (Fig 1): (A) channels which are intrinsic structures of the receptor (receptor-operated channels), (B) channels which are coupled to receptors via a G-protein (G-protein-operated channels), (C) channels which are activated by some second messengers (second-messenger-operated channels), and (D) channels which open upon intracellular nonmitochondrial Ca²⁺ store depletion (Ca²⁺ release-activated channels) resulting from inositol 1, 4, 5-trisphosphate-induced Ca²⁺ release or inhibition of Ca²⁺ re-uptake (see next section). Ca²⁺ entry via the 4th type of channel, also known as "capacitative Ca²⁺ entry" (CCE)[4], has aroused much interest in the past decade because of its intriguing nature as retrograde signalling. In this brief review, we present the evidence for and the possible biochemical processes involved in CCE. We also discuss the use of 2 novel Ca²⁺ entry blockers: tetrandrine and SK&F 96365. Emphasis will be put on the human leukemic HL-60 cell line, a popular cell system for intracellular Ca²⁺ homeostasis studies and also a model the signal transduction of which we have been investigating during the past few years.