Activation of adenylyl cyclase down-regulates sodium-calcium
exchanger of arterial myocytes.
Smith, Lucinda, and Jeffrey Bingham Smith.
Department of Pharmacology and Toxicology, Schools of Medicine and
Dentistry, University of Alabama at Birmingham, Birmingham, Alabama
35294-0019
APStracts 2:0248C, 1995.
Chronic elevation of cyclic AMP is known to inhibit the proliferation
of cultured vascular smooth muscle cells. The present findings show
that the activation of adenylyl cyclase with forskolin decreased
Na&-Ca2& exchanger (NCX) mRNA and activity. Fetal bovine serum
restored NCX transcript and activity. The changes in NCX transcript
preceded the changes in NCX activity. Incubation of low passage,
immortalized myocytes with forskolin plus methylisobutyl xanthine
(MIX), which inhibits cyclic AMP phosphodiesterase, decreased NCX
mRNA by 60% in 6 h and 80% in 24 h. After a 6 h lag, forskolin plus
MIX decreased NCX activity almost linearly to 20% control at 40 h.
Dideoxyforskolin, which does not activate adenylyl cyclase, had no
effect on NCX mRNA or activity. Forskolin plus MIX decreased the c
-Myc transcript, an immediate- early gene whose expression correlates
with cell proliferation, but had no effect on plasma membrane Ca2&
ATPase transcripts. Removal of forskolin plus MIX and addition of
fetal bovine serum increased NCX and c-Myc transcripts 7-8 fold in 6
h, and restored NCX activity in 24 h. Inhibition of protein or RNA
synthesis by cycloheximide or actinomycin D, respectively, prevented
the increase in NCX mRNA. In contrast to blocking NCX induction,
cycloheximide potentiated c-Myc induction by serum. Transcription
factors that regulate myocyte growth may mediate the opposing
influences of serum and forskolin on NCX mRNA and activity.
Received 8 March 1995; accepted in final form 14 June 1995
APS Manuscript Number C0131-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.