The interdependence of endothelin-I and calcium: a review

The 21-amino-acid peptide ET-I (endothelin-I) regulates a diverse array of physiological processes, including vasoconstriction, angiogenesis, nociception and cell proliferation. Most of the effects of ET-I are associated with an increase in intracellular calcium concentration. The calcium influx and mobilization pathways activated by ET-I, however, vary immensely. The present review begins with the basics of calcium signalling and investigates the different ways intracellular calcium concentration can increase in response to a stimulus. The focus then shifts to ET-I, and discusses how ET receptors mobilize calcium. We also examine how disease alters calcium-dependent responses to ET-I by discussing changes to ET-I-mediated calcium signalling in hypertension, as there is significant interest in the role of ET-I in this important disease. A list of unanswered questions regarding ET-mediated calcium signals are also presented, as well as perspectives for future research of calcium mobilization by ET-I.