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, lung, intestine, kidney, liver, spleen, skeletal muscle and fat. The synthesis 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 after hormonal stimulation and no cyclic PIP can be detected in urine. As an indication of its ubiquity, cyclic PIP was even detected in yeast. Prostaglandin E (as shown by incorporation of [3H]PGE into cyclic PIP and demonstration of a constant specific activity), myo-inositol (as shown by acid hydrolysis of the dephosphorylated cyclic PIP and mass spectrometric identification of the products) and one phosphate (as shown by the ionic nature of cyclic PIP and its inactivation by phosphodiesterase plus phosphatase) are components of cyclic PIP. Chemical derivatization experiments of cyclic PIP suggest the phosphate to be bound to myo-inositol and the myo-inositol phosphate to the prostaglandin E by its C15-hydroxyl group.
Wasner
H K
HK
Diabetes-Forschungsinstitut, Düsseldorf, Germany.
Salge
U
U
Gebel
M
M
D000818:Animals; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D000242:Cyclic AMP / Q000037:antagonists & inhibitors*; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D009638:Norepinephrine / Q000494:pharmacology; D009928:Organ Specificity; D010656:Phenylephrine / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D007295:Inositol Phosphates; D007328:Insulin; D010710:Phosphates; D011458:Prostaglandins E; C052775:prostaglandin-inositol cyclic phosphate; D010656:Phenylephrine; D007294:Inositol; D000242:Cyclic AMP; D011972:Receptor, Insulin; D009638:Norepinephrine