Is Up-Regulation of Phosphodiesterase 4 Activity by PGE2Involved in the Desensitization of β-Mimetics in Late Pregnancy Human Myometrium?
| Autor: | Marie-Josèphe Leroy, G. Tanguy, Dominique Cabrol, Céline Méhats, Françoise Ferré, Emmanuelle Dallot |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
medicine.medical_specialty Prostaglandin Antagonists Phosphodiesterase Inhibitors Pyridines Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Stimulation In Vitro Techniques Biology Biochemistry Cyclase Dinoprostone Endocrinology PDE4B Downregulation and upregulation Pregnancy Oxytocics Internal medicine Cyclic AMP medicine Humans Albuterol Prostaglandin E2 Cells Cultured Desensitization (medicine) Reverse Transcriptase Polymerase Chain Reaction Biochemistry (medical) Myometrium Proteins Phosphodiesterase Adrenergic beta-Agonists Immunohistochemistry Cyclic Nucleotide Phosphodiesterases Type 3 Cyclic Nucleotide Phosphodiesterases Type 4 Up-Regulation Isoenzymes 3' 5'-Cyclic-AMP Phosphodiesterases Benzamides Female Muscle Contraction medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 86:5358-5365 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.86.11.7989 |
| Popis: | Elevation of cAMP content resulting from stimulation of the receptor-adenylyl cyclase complex is involved in maintaining the quiescence of the human myometrium during pregnancy. The magnitude of this elevation is critically influenced by the rate of cAMP hydrolysis by phosphodiesterase (PDE) isoenzymes. In the present study we report that in term myometrium, enhanced cAMP-specific PDE4 activity takes part in the heterologous desensitization to the beta-mimetic, salbutamol. Indeed, pretreatment with a PDE4-selective inhibitor potentiates the relaxant effect of salbutamol on myometrial strips of women at term. Furthermore, the reduced relaxant effect of salbutamol after long-term treatment of myometrial strips with PGE2, a potent myometrial effector, can be reversed by PDE4 inhibition. Using a model of cultured myometrial cells, we also demonstrated that PGE2 is able to up-regulate PDE4 activity, at least through the induction of synthesis of PDE4B and PDE4D short forms, which, in turn, dampen the cAMP accumulation provoked by the stimulation of adenylyl cyclase. Such data suggest that in late pregnancy endogenous PGE2 might up-regulate PDE4 activity and lessen the responsiveness of myometrium to beta-mimetic activation. Accordingly, coapplication of a selective PDE4 inhibitor might greatly improve the usefulness of beta-mimetic in tocolysis. |
| Databáze: | OpenAIRE |
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