Myocardial production of prostaglandins: its role in atrial natriuretic peptide release.
In recent years, considerable evidence has been accumulated on prostaglandins (PG) in modulating atrial natriuretic peptide (ANP) release. In the current study we investigated whether eicosanoids promote isoproterenol-induced ANP secretion from superfused rabbit sliced atria. Inclusion of the cyclooxygenase inhibitor indomethacin (10 mumol) to the superfusing medium abolished isoproterenol-induced ANP release. Next, PGE2, but not PGF2 alpha or PGI2 (10 mumol), increased ANP release. Furthermore, isoproterenol-induced PGE2 formation was fully attenuated by indomethacin. Dibutyl-cAMP (0.5 mmol) had no effect on PGE2 formation, and the protein kinase A (PKA) inhibitor H89 (20 mumol) did not alter isoproterenol-induced PGE2 formation. On the other hand, indomethacin led to a significant decrease in isoproterenol-induced cAMP production. In addition, PGE2 enhanced basal cAMP concentration in superfusates. Superfusion of sliced atria by forskolin (10 mumol) or by dibutyl-cAMP (0.5 mmol) produced a significant rise in ANP release. Finally, H89 was ineffective on basal ANP release but abolished the increase of ANP release in response to isoproterenol or to PGE2. We conclude that: the effect of isoproterenol on ANP release is sensitive to indomethacin and H89; PGE2, but not PGE2 alpha or PGI2, increases ANP release; isoproterenol promotes myocardial PGE2 formation independently of adenylate cyclase and PKA activation pathways; and PGE2-induced ANP release is mediated by cAMP production and subsequent PKA activation. These results suggest that isoproterenol-induced ANP release appears to be mediated at least partly by PGE2 with underlying cAMP formation and PKA activation.
Azizi
C
C
Service de Biochimie, CHU Pitié-Salpêtrière, Paris, France.
Barthélemy
C
C
Masson
F
F
Maistre
G
G
Eurin
J
J
Carayon
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006325:Heart Atria; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits
D011453:Prostaglandins; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol