Subtype-specific roles of cAMP phosphodiesterases in regulation of atrial natriuretic peptide release.
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.
Cui
Xun
X
Department of Physiology, Medical School, Institute for Medical Sciences, Jeonbug National University, Jeonju 561-180, South Korea.
Wen
Jin Fu
JF
Jin
Hua
H
Li
Dan
D
Jin
Jing Yu
JY
Kim
Suhn Hee
SH
Kim
Sung Zoo
SZ
Lee
Ho Sub
HS
Cho
Kyung Woo
KW
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
D010726:Phosphodiesterase Inhibitors; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases