CALCIUM INFLUX AND PROTEIN-KINASE C-ALPHA ACTIVATION MEDIATE ARACHIDONIC-ACID MOBILIZATION BY THE HUMAN NK-2 RECEPTOR EXPRESSED IN CHINESE-HAMSTER OVARY CELLS

We have cloned a cDNA encoding the human ileal neurokinin-2 (NK-2) rec eptor which mediates powerful neurokinin A-stimulated arachidonic acid (AA) and prostaglandin release when expressed in CHO cells. Two major signal transduction events appear to underlie this response. Firstly, AA liberation is critically dependent upon agonist-stimulated influx of extracellular Ca2+ although not release from intracellular stores. Secondly, NK-2 receptor-linked AA mobilization requires concomitant PK C activation and based upon limited subtype immunodetectability as wel l as NKA-stimulated translocation, PKC alpha could play a major role. While NKA-stimuIated Ca2+ mobilization is insensitive to preincubation with pertussis toxin, identical pretreatment inhibits AA release part ially and blocks PKC alpha translocation completely. These observation s indicate that in this cell system AA liberation reflects NK-2 recept or-dependent activation of two distinct but converging signal transduc tion pathways regulated by different G-protein species and involving C a2+ influx and PKC alpha activation.