Pharmacology of receptor operated calcium entry in human neutrophils

In neutrophils, increases in intracellular calcium [Ca(2+)](i) provide a crucial link between inflammatory mediators and inflammatory responses. The modulation of [Ca(2+)](i) fluxes in non-excitable cells such as neutrophils has been studied for more than 25 years yet remains to be resolved. In these cells, the Ca(2+) influx can occur through at least two mechanisms, as follows: one dependent on the state of filling of the endoplasmic reticulum Ca(2+) stores, termed store operated calcium entry (SOCE), and the other less studied mechanism in neutrophils which is not dependent on the state of the Ca(2+) stores but is regulated by receptor occupation, termed receptor operated calcium entry (ROCE). Over the past ten years, the molecular components of SOCE have been extensively characterized, but in neutrophils, the molecular components of ROCE have only recently been explored. In this review, we discuss recent research findings that have demonstrated an important role for ROCE in human neutrophils. In addition, an overview of pharmacological approaches used to discriminate between ROCE and SOCE will be discussed. The elucidation of the molecular components of ROCE may well provide important pharmacological targets for the development of novel anti-inflammatory drugs.