SMOOTH MUSCLE CELL ARACHIDONIC ACID RELEASE, MIGRATION, AND PROLIFERATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pharmacologic evidence suggests that the lipid products generated by one or more Ca2+-independent phospholipases A2 (iPLA2s) participate in the regulation of vascular tone through smooth muscle cell (SMC) Ca2+ signaling and the release of arachidonic acid. However, the recent identification of new members of the iPLA2 family, each inhibitable by (E)-6-(bromomethyl ene)-3-(1-naphthal enyl )- 2 H- t e t r a hy dr o py r a n- 2 - one, has rendered definitive identification of the specific enzyme(s) mediating these processes difficult. Accordingly, we used iPLA2b-/- mice to demonstrate that iPLA2b is responsible for the majority of thapsigargin and ionophore (A23187)-induced arachidonic acid release from SMCs.