THE SOMATOSTATIN RECEPTOR SSTR1 IS COUPLED TO PHOSPHOTYROSINE PHOSPHATASE-ACTIVITY IN CHO-K1 CELLS

Somatostatin receptors are abundantly expressed on a variety of human endocrine and epithelial tumors. The ability of these receptors to cou ple to effector pathways that inhibit the growth of these tumor cells has prompted the use of somatostatin agonists in the treatment of huma n neoplasms. It has been demonstrated that somatostatin stimulates a p hosphotyrosine phosphatase in human tumor cells through a receptor-med iated process. This stimulation may counteract the growth-promoting pr operties of growth factors and the receptor tyrosine kinases that they activate. The recent cloning and characterization of distinct somatos tatin receptor subtypes raise the possibility that different receptor subtypes mediate distinct effector pathways. To determine whether clon ed somatostatin receptors could mediate coupling to phosphotyrosine ph osphatase activity, we examined phosphatase activity after somatotosta tin activation of the rat somatostatin receptors SSTR1 and SSTR2 after their stable expression in heterologous Chinese Hamster Ovary (CHO-K1 ) cells. We found that stimulation of SSTR1 cells was capable of incre asing phosphotyrosine phosphatase activity, despite the coupling of bo th receptors to the inhibition of adenylyl cyclase in these cells. Thi s activation was characterized by an EC(50) of 70 nM and was sensitive to pertussis toxin. In addition, we demonstrate that activation of ph osphotyrosine phosphatase activity in pituitary cell lines correlates with the endogenous expression of the SSTR1 gene within these cells.