Caloxin 1b1 is obtained by screening for binding to extracellular domain 1 of PMCA4, which inhibited PMCA extracellularly, selectively, and had a higher affinity for PMCA4 than PMCA1. Because caloxin 1b1 had been selected to bind to an extracellular domain of PMCA, it could be added directly to cells and tissues to examine its effects on smooth muscle and endothelium.