ON THE MECHANISM OF CYTOSOLIC PHOSPHOLIPASE A(2) ACTIVATION IN CHO CELLS CARRYING SOMATOSTATIN RECEPTOR - WORTMANNIN-SENSITIVE PATHWAY TO ACTIVATE MITOGEN-ACTIVATED PROTEIN-KINASE

We examined the mechanism of arachidonate release induced by somatosta tin-14 (SS14) in CHO-K1 cells overexpressing rat hippocampal somatosta tin receptor SSTR4. SSTR4 couples to pertussis toxin (PTX)-sensitive G -protein in CHO cells and does not lead to phosphoinositides breakdown or intracellular calcium ([Ca2+]i) mobilization (Bite et al.: J. Biol . Chem. 269, 12722-12730, 1994). SSTR4 activated mitogen-activated pro tein (MAP) kinase and induced the phosphorylation of 85kDa cytosolic p hospholipase A(2) (cPLA(2)), in a PTX-sensitive manner. Furthermore, a ctivations of both MAP kinase and cPLA(2) were inhibited by treatment with wortmannin, at almost identical IC50 values. Thus, SSTR4 appears to stimulate MAP kinase and cPLA(2) in a Gi-dependent, and through a w ortmannin-sensitive pathway. We also showed that stimulation with SS14 , in combination with calcium-ionophore, strongly enhanced arachidonat e release from these cells. (C) 1994 Academic Press, Inc.