Role of camp and calcium influx in endothelin-1-induced anp release
in rat cardiomyocytes.
Rebsamen, M. C., D. J. Church, D. Morabito, M. B. Vallotton, and U.
Lang.
Division of Endocrinology and Diabetology, University Hospital, CH
-1211 Geneva 14, Switzerland, and Geneva Biomedical Research
Institute, CH-1211 Geneva 14, Switzerland.
APStracts 4:0172E, 1997.
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 (Kd = 54 +/- 18 pM, n=3), but no ETB receptors.
Incubation of cardiomyocytes with ET-1 led to concentration-dependent
ANP release and prostacyclin (PGI2) production. ET-1-induced ANP
release was neither affected by 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 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. 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.
Received 6 February 1997; accepted in final form 24 July 1997.
APS Manuscript Number E54-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997