Mechanisms of isoproterenol-induced atrial natriuretic peptide release from superfused rabbit atria.
The mechanisms for isoproterenol-induced atrial natriuretic peptide (ANP) release were studied in superfused rabbit sliced right atria. Addition of 1 microM norepinephrine to this preparation induced a significant monophasic twofold rise in ANP release. This effect was abolished by 1 microM propranolol and mimicked by 1 microM isoproterenol. Furthermore, addition of 200 microM 3-isobutyl-1-methylxanthine (IBMX) to the superfusing medium potentiated isoproterenol effect 31%. In addition, superfusion of slices with 0.5 mM N6,2-O-dibutyryladenosine 3',5'-cyclic monophosphate [(Bu)-2cAMP] enhanced ANP release in the same manner as the beta-agonist. After isoproterenol stimulation, adenosine 3',5'-cyclic monophosphate (cAMP) concentration in effluents increased significantly. ANP secretory response to isoproterenol was unaffected by extracellular calcium concentration or 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Finally, 10 microM indomethacin significantly reduced isoproterenol-stimulated ANP release. It is concluded that 1) norepinephrine-induced ANP release is mediated by its beta-agonist activity, 2) isoproterenol-stimulated release appears to be mediated by cAMP, 3) isoproterenol effect does not require extracellular calcium, and 4) prostaglandins may be involved in this beta-adrenergic effect.
Azizi
C
C
Service de Biochimie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Carayon
A
A
Masson
F
F
Noé
E
E
Barthelemy
C
C
Eurin
J
J
Maistre
G
G
Legrand
J C
JC
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006325:Heart Atria; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits
D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine