• Citer

Modulation of cyclic AMP action in the dog thyroid by its agonist and antagonist Sp- and Rp-adenosine 3',5'-monophosphorothioate.

par Erneux, Christophe ;Van Sande, Jacqueline ;Jastorff, B;Dumont, Jacques Emile
Référence Biochemical journal, 234, 1, page (193-197)
Publication Publié, 1986-02

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

The diastereoisomeric forms of adenosine 3',5'-monophosphorothioate, Sp-cAMPS and Rp-cAMPS, have been shown to mimic and to inhibit activation of protein kinase type I and type II by cyclic AMP. In the present work, Sp-cAMPS mimicked thyrotropin (TSH) action on thyroid hormone secretion and protein iodination in dog thyroid slices, whereas Rp-cAMPS antagonized those effects. The phosphorothioates have been tested as inhibitors or activators of the three major phosphodiesterases: the Ca2+/calmodulin-sensitive form, the cyclic GMP-stimulated form and the cyclic AMP-specific enzyme. At 100 microM Sp-cAMPS inhibited the three enzyme activities. In contrast, Rp-cAMPS failed to stimulate activity of the three enzymes. From a comparison of the biological properties of Sp- and Rp-cAMPS and 3-isobutyl-1-methyl xanthine, it is suggested that one site of action of the phosphorothioates is on the cyclic AMP-dependent protein kinases, i.e. the effects of Sp-cAMPS and Rp-cAMPS observed in intact cell can be ascribed to the agonistic and antagonistic effects on the cyclic AMP-dependent protein kinases. However, partial inhibition of phosphodiesterase activities by the phosphorothioates cannot be excluded.