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) receptor 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 PKC activation and based upon limited subtype immunodetectability as well 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 partially and blocks PKC alpha translocation completely. These observations indicate that in this cell system AA liberation reflects NK-2 receptor-dependent activation of two distinct but converging signal transduction pathways regulated by different G-protein species and involving Ca2+ influx and PKC alpha activation.