Cyclic GMP stimulates inositol phosphate production in cultured pituitary cells: Possible implication to signal transduction

Addition of the stable and permeable analog 8-bromo cyclic GMP (8-BR-cGMP) to myo-[2-³H]inositol prelabeled cultured rat pituitary cells results in enhanced formation of [³H]-myo-inositol monophosphate (IP₁). The stimulatory effect of the cyclic nucleotide analog is additive to the effect of Li⁺, which accumulates IP₁ via inhibition of inositol 1-monophosphatase, and also to the effect of gonadotropin releasing hormone (GnRH) which stimulates the formation of IP₁, as welll as that of inositol 1,4-bisphosphate (IP₂) and inositol 1,4,5-trisphosphate (IP₃) via enhanced hydrolysis of polyphosphoinositides. Many Ca²⁺-mobilizing hormones acting via phosphoinositide turnover also stimulate cGMP formation. The cyclic nucleotide might then serve as a modulator by further hydrolysis of phosphoinositides needed for protein kinase C activation.