Stimulation of atrial natriuretic peptide release by neurokinins in
neonatal rat ventricular cardiomyocytes.
Church, Dennis J., Stephen J. Arkinstall, Michel B. Vallotton,
Angelika Chollet, Eric Kawashima, and Ursula Lang.
Department of Medicine, Division of Endocrinology, University
Hospital, CH-1211 Geneva 4, Switzerland and # The Glaxo Institute for
Molecular Biology, 1228, Plan-les-Ouates, Geneva Switzerland
APStracts 2:0452H, 1995.
The effect of substance P (SP) on ANP release was studied in neonatal
rat ventricular cardiomyocytes. Incubation of cells with SP led to a
marked increase in ANP secretion, a response accompanied by increases
in a-type protein kinase C (PKC) in the membranous cell fraction, 6
-keto-prostaglandin F1a (6-keto-PGF1a) formation, and a small increase
in cAMP production. A role for PKC in SP-induced 6-keto-PGF1a
formation and ANP release was apparent insofar as the responses were
supressed by PKC inhibitors and in PKC down-regulated cells.
Furthermore, SP-induced 6-keto-PGF1a production was strongly
correlated with SP-induced ANP secretion (r = 0.91, p < 0.0001,
n = 27), suggesting a role for prostaglandins in SP-mediated ANP
release. Supporting this, indomethacin abolished SP-induced ANP
release, while prostaglandins E2 and F2a (PGE2 and PGF2a) and
prostacyclin (PGI2) promoted ANP secretion in this system. Both the
profile of SP-induced cAMP production and results obtained with
prostaglandin antagonists suggest that a prostanoid FP receptor is at
the basis of this response. Finally, both neurokinin A (NKA) and
neurokinin B (NKB) induced similar ANP responses, while cultured
cells were found to contain mRNA transcripts coding for both NK-1 and
NK-3 neurokinin receptor subtypes. Overall, these results suggest
that SP induces ANP secretion in neonatal ventricular cardiomyocytes
through a PKC and prostaglandin-dependent signalling pathway.
Received 6 May 1994; accepted in final form 15 August 1995.
APS Manuscript Number H401-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95