Endothelin-1 stimulates atrial natriuretic peptide release in ventricular cardiomyocytes via an ETA receptor-mediated pathway involving cAMP formation and a nifedipine-sensitive calcium channel.
This study elucidates that endothelin-1 induces ANP release in ventricular cardiomyocytes via cAMP formation and calcium influx rather than PKC or prostaglandin pathways.
The mechanism of endothelin-1 (ET-1)-induced atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. These cells expressed a single high-affinity class of ETA receptor (dissociation constant = 54 +/- 18 pM, n = 3), but no ETB receptors. Incubation of cardiomyocytes with ET-1 led to concentration-dependent ANP release and prostacyclin production. ET-1-induced ANP release was affected by neither protein kinase C (PKC) inhibition or downregulation nor by cyclooxygenase inhibition, indicating that ET-1-stimulated ANP secretion is not a PKC-mediated, prostaglandin-dependent process. Furthermore, ET-1 significantly stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production and increased cytosolic calcium concentration in these preparations. Both ET-1-induced calcium influx and ANP release were decreased by the cAMP antagonist Rp-cAMPS, the Rp diastereoisomer of cAMP. Moreover, ET-1-induced ANP secretion was strongly inhibited in the presence of nifedipine as well as in the absence of extracellular calcium. Thus our results suggest that ET-1 stimulates ANP release in ventricular cardiomyocytes via an ETA receptor-mediated pathway involving cAMP formation and activation of a nifedipine-sensitive calcium channel.
Rebsamen et al. (1997) studied this question. Endothelin-1 (ET-1) was evaluated on Atrial natriuretic peptide (ANP) release. Endothelin-1 stimulates atrial natriuretic peptide release in ventricular cardiomyocytes via an ETA receptor-mediated pathway involving cAMP formation and a nifedipine-sensitive calcium channel.