PHORBOL ESTER ACTIVATION OF PROTEIN-KINASE-C INHIBITS CNP-STIMULATED CYCLIC-GMP PRODUCTION IN THE MOUSE ATT-20 PITUITARY-TUMOR CELL-LINE

Preincubation of AtT-20 mouse pituitary tumour cells with the phorbol ester PMA resulted in a concentration-dependent inhibition of CNP-stim ulated cyclic GMP production. The phorbol ester analogue 4 alpha phorb ol had no inhibitory effect and 24 h preincubations with PMA resulted in a characteristic down-regulation of the response indicating that th e inhibitory actions were mediated via the activation of protein kinas e C. Forskolin in the presence of the phosphodiesterase inhibitor IBMX stimulated intracellular cyclic AMP concentrations by up to eight fol d, but did not alter basal nor CNP-stimulated cyclic GMP production. T hese results indicate that CNP-stimulated guanylate cyclase activity a ssociated with the GC-B natriuretic peptide receptor expressed in AtT- 20 cells is inhibited by protein kinase C. (C) 1994 Academic Press, In c.