THE ENDOGENOUS CYCLIC-AMP ANTAGONIST, CYCLIC PIP - ITS UBIQUITY, HORMONE-STIMULATED SYNTHESIS AND IDENTIFICATION AS PROSTAGLANDYLINOSITOL CYCLIC PHOSPHATE

This report shows that the cyclic AMP antagonist cyclic PIP is present in all organs and tissues of the rat so far examined: brain, heart, l ung, intestine, kidney, liver, spleen, skeletal muscle and fat. The sy nthesis of cyclic PIP is stimulated by insulin or noradrenaline (alpha -adrenergic action) in a dose-dependent fashion. Increasing cyclic PIP synthesis with increasing insulin concentrations matches the insulin receptor binding curves. Cyclic PIP levels in blood serum remain low a fter hormonal stimulation and no cyclic PIP can be detected in urine. As an indication of its ubiquity, cyclic PIP was even detected in yeas t. Prostaglandin E (as shown by incorporation of [H-3]PGE into cyclic PIP and demonstration of a constant specific activity), myo-inositol ( as shown by acid hydrolysis of the dephosphorylated cyclic PIP and mas s spectrometric identification of the products) and one phosphate (as shown by the ionic nature of cyclic PIP and its inactivation by phosph odiesterase plus phosphatase) are components of cyclic PIP. Chemical d erivatization experiments of cyclic PIP suggest the phosphate to be bo und to myo-inositol and the myo-inositol phosphate to the prostaglandi n E by its C-15-hydroxyl group.