HETEROGENEITY OF CAFFEINE-SENSITIVE AND BRADYKININ-SENSITIVE CA2-CELLS( STORES IN VASCULAR ENDOTHELIAL)

The filling state of Ca2+ stores in endothelial cells regulates Ca2+ e ntry. The functional relationship between the major Ca2+ stores [i.e. Ins(1,4,5)P-3-sensitive (= bradykinin-sensitive stores,'BsS') and caff eine-sensitive stores] is unknown. In pig right-coronary-artery endoth elial cells, caffeine failed to release Ca2+ in 68% of the cells (quie t-responders), but increased bradykinin (Bk)induced Ca2+ release 2.5-f old. In Bk-pre-stimulated cells, caffeine increased Ca2+ release upon a second stimulation with Bk 3.2-fold. In quiet-responders caffeine al one did not affect net Ca2+ storage, whereas Bk or caffeine followed b y Bk decreased the intracellular Ca2+ pool to 45% and 15%, respectivel y. Blockade of the endoplasmic-reticulum Ca2+ pump by thapsigargin unm asked the effect of caffeine in quiet-responders, resulting in a trans ient increase in intracellular free Ca2+ concentration ([Ca2+](i)). In 37% of the cells caffeine alone transiently increased [Ca2+](i) and d epleted BsS. This study suggests a heterogeneity in functional organiz ation of endothelial Ca2+ stores. In quiet-responders, caffeine transl ocates Ca2+ towards the BsS, whereas in overt-responders caffeine empt ies the BsS.