title: Subtype-specific roles of cAMP phosphodiesterases in regulation of atrial natriuretic peptide release.
abstract: cAMP is known to control the release of atrial natriuretic peptide. To define the roles of cyclic nucleotide phosphodiesterase subtypes in the regulation of atrial natriuretic peptide (ANP) release, experiments were done with perfused beating rabbit atria. Phosphodiesterase 3 subtype-specific inhibitors, milrinone and cilostamide, inhibited myocytic ANP release with a concomitant increase in cAMP efflux. Similarly, trequinsin, another phosphodiesterase 3 inhibitor, decreased ANP release. A phosphodiesterase 4 subtype-specific inhibitor, rolipram, did not significantly change ANP release but increased AMP efflux. Also, 4-[(3-butoxy-4-methoxyphenyl)methyl]-2-imidazolidinone (Ro 20-1724), another phosphodiesterase 4 inhibitor, did not significantly change ANP release. The cAMP efflux was higher in the atrium treated with rolipram than in the atrium treated with milrinone or cilostamide. The data show that the cAMP pool, which is metabolized by phosphodiesterase 3, but not phosphodiesterase 4, is closely related to the basal regulation of atrial ANP release. The results suggest that intracellular cAMP is compartmentalized in the regulation of atrial ANP release, and that the release is controlled by a phosphodiesterase subtype-specific mechanism.
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Jeonbug National University, Jeonju 561-180, South Korea.
authors.forename: Xun
authors.initials: X
authors.lastname: Cui
authors.forename: Jin Fu
authors.initials: JF
authors.lastname: Wen
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Jin
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Zoo
authors.initials: SZ
authors.lastname: Kim
authors.forename: Ho Sub
authors.initials: HS
authors.lastname: Lee
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Cho
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000145:classification / Q000502:physiology*; D011817:Rabbits; D011863:Radioimmunoassay; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D010726:Phosphodiesterase Inhibitors; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases