We studied the role of the Pmrl-containing Ca2+ store in COS-1 cells endowed with a functional endoplasmic reticulum. Transfected cells could be recognized by using a green-fluorescent-protein (GFP)-tagged form of Pmrl. Pmrl-GFP fluorescence showed a typical juxtanuclear Golgi-like distribution. Pmrl-GFP-containing cells with functional endoplasmic reticulum responded to 100 muM ATP with baseline Ca2+ spiking, while non-transfected cells produced an initial Ca2+ peak followed by a long-lasting plateau. The Ca2+ signal often appeared after a long latency in Pmrl-GFP-expressing cells. ATP-stimulated Pmrl-GFP-expressing cells with functional endoplasmic reticulum responded after a latency period to extracellular Ca2+ with a regenerative Ca2+ signal, while non-transfected control cells responded with an immediate slow rise in free cytosolic Ca2+ concentration. These results demonstrate the importance of the Pmrl-containing Ca2+ store in generating or modifying cellular Ca2+ signals. (C) 2002 Elsevier Science (USA). All rights reserved.