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F Miot

Publications and source records attributed to F Miot.

24 records · Page 2Linked to original sources
PubMed1985

The binding of cyclic nucleotide analogs to a purified cyclic GMP-stimulated phosphodiesterase from bovine adrenal tissue.

The specificity of binding of [3H]cGMP to purified bovine adrenal cGMP-stimulated phosphodiesterase was investigated by adding increasing concentrations of unlabelled analogs of cAMP and cGMP. The data show a perfect correlation between the potencies of stimulation of cAMP phosphodiesterase activity and displacement curves of [3H]cGMP binding. Since the Sp and Rp diastereomers of adenosine 3',5'-monophosphate behaved as a cAMP-dependent protein kinase agonist and antagonist, respectively, the possible biological activity of these compounds and the corresponding cGMP analogs (cGMPS Sp and Rp) on the cGMP-stimulated phosphodiesterase was investigated. The data show no regioselectivity in binding nor on activation of one of the two (Sp) or (Rp) isomers.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1984

The effects of alkylated xanthines on cyclic AMP accumulation in dog thyroid slices exposed to carbamylcholine.

In dog thyroid slices stimulated by thyrotropin (TSH), activation of muscarinic cholinergic receptors leads to a decrease in cyclic AMP levels. Previous studies have established that carbamylcholine enhances cyclic GMP levels and inhibits cyclic AMP accumulation. Several experimental data have suggested that these effects are mediated by an increase in intracellular Ca2+ levels. The inhibition of cyclic AMP accumulation results in accelerated catabolism. Dog thyroid phosphodiesterase activity is due to a mixture of three enzyme forms: a calmodulin-sensitive form, a cyclic GMP-stimulated form and a cyclic AMP-specific form. This report is concerned with the comparison of the effects of several phosphodiesterase inhibitors on cell-free phosphodiestease activity and on cyclic nucleotide accumulation in intact cells. Alkylated xanthines, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724), and 2-O-propoxyphenyl-8-azapurin-6-one (M & B 22948) were studied as inhibitors of partially purified dog thyroid phosphodieterases and for their ability to alter cyclic AMP and cyclic GMP accumulation in dog thyroid slices that had been stimulated with TSH and/or carbamylcholine. 1-Methyl-3-isobutylxanthine (MIX) and 7-benzyl MIX were the most potent inhibitors of phosphodiesterase activities in the crude soluble and particulate fractions but exhibited no selectivity for inhibiting cyclic AMP or cyclic GMP hydrolysis. In dog thyroid slices stimulated by TSH and in the absence of carbamylcholine, Ro 20-1724 and 1-isoamyl-3-isobutylxanthine (IIX) were the most effective compounds to potentiate the accumulation of cyclic AMP. The rank order of abilities to potentiate cyclic AMP accumulation in dog thyroid slices stimulated by TSH paralleled the rank order of potencies to inhibit the cyclic AMP-specific phosphodiesterase. In the presence of carbamylcholine, the observed decrease in cyclic AMP levels was attenuated by MIX, 8-methoxymethyl MIX (8-MeOMe MIX), 7-benzyl MIX, and M & B 22948, the most potent inhibitors of the calmodulin-sensitive phosphodiesterase. MIX, 8-MeOMe MIX, and 7-benzyl MIX inhibited the cyclic GMP-stimulated phosphodiesterase in the same rank order of potencies as the calmodulin-sensitive enzyme, but M & B 22948 did not significantly inhibit the cyclic GMP-stimulated enzyme activity. IIX and Ro 20-1724 did not alter the carbamylcholine-induced inhibition of cyclic AMP accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Characterization of the soluble cyclic nucleotide phosphodiesterases in Xenopus laevis oocytes. Evidence for a calmodulin-dependent enzyme.

Cyclic nucleotide phosphodiesterase activities (3',5'-cyclic nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) were found in the 40,000 X g supernatant fraction of homogenates of Xenopus laevis oocytes. In the supernatant, the ratio of the specific activity of cyclic AMP phosphodiesterase to that of cyclic GMP phosphodiesterase was 1.1 at the 1 micro substrate level. Two phosphodiesterase forms were isolated by centrifugation on sucrose gradient: a 3-4 S form hydrolyzing specificity cyclic AMP and a 6-7 S form hydrolyzing both cyclic nucleotides (cyclic AMP and cyclic GMP). The activity of the 6-7 S phosphodiesterase was characterized by its activation by 0.1 micro M calmodulin purified from beef pancreas in the presence of 50 micro M CA2+. The calmodulin dependence of this form was completely abolished in the presence of 1 mM ethyleneglycobis(beta-aminoethyl ether)-N-N,N',N'-tetraacetic acid (EGTA). Trifluoperazine at 0.1 mM inhibited both the freshly prepared crude enzyme and the partially purified 6-7 S form. On the other hand, no effect of cyclic GMP at 3 micro M was observed on cyclic AMP hydrolysis in the case of the supernatant or that of the partially purified phosphodiesterases. These data show the presence of a calmodulin-dependent phosphodiesterase in the soluble fraction of X. laevis oocytes.

3',5'-Cyclic-AMP Phosphodiesterases↗