Cellular Signalling 1993-09-01

Isobutylmethylxanthine and other classical cyclic nucleotide phosphodiesterase inhibitors affect cAMP-dependent protein kinase activity.

C Tomes, S Rossi, S Moreno

Index: Cell. Signal. 5(5) , 615-21, (1993)

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Abstract

The effect of 17 inhibitors of cyclic nucleotide phosphodiesterases (PDEs) was assayed on cAMP binding activity of Mucor rouxii protein kinase A (PKA), on PKA activity in the absence of cAMP and on free catalytic subunit (C) activity. Isobutylmethylxanthine (IBMX), SQ 20,009 and cilostamide, at 0.2 mM, behaved as partial agonists of cAMP since they inhibited binding of 0.15 microM [3H]cAMP to the regulatory subunit (R), stimulated slightly PKA activity in the absence of cAMP and did not modify C activity. Amrinone at 0.2 mM inhibited C activity competitively towards ATP. These four compounds displayed the same effects when assayed on eukaryotic protein kinase A types I (PKI) and II (PKII). The combined effect of IBMX and cAMP was analysed on Mucor PKA. Under dissociating conditions (+ 0.5 M NaCl) IBMX antagonized activation by low concentrations of cAMP, while in the absence of NaCl, IBMX potentiated the stimulating activity of cAMP.