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Volume 270,
Number 18,
Issue of May 5, pp. 11012-11016, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
/
-Adrenergic Receptor-coupled
Adenylyl Cyclase System in Rat Myometrium during Pregnancy
- and
-adrenoreceptors (AR),
identified by Northern blotting in rat myometrium, showed a
differential expression during the course of pregnancy. Indeed, the
-AR transcript was present at mid-pregnancy, whereas
high levels of
-AR mRNA could be detected at term.
The role of these subtypes in modulating
-AR-stimulated adenylyl cyclase activity was
investigated on myometrial membranes from mid-pregnancy and term. At
nanomolar concentrations of clonidine (full -AR
agonist) or oxymetazoline (partial -AR agonist),
adenylyl cyclase activity was inhibited by up to 50 ± 7% at
mid-pregnancy or 75 ± 7% at term, whereas at micromolar
concentrations,
-AR agonists potentiate adenylyl
cyclase activity by 140-170% at mid-pregnancy. Both inhibitory
and stimulatory components of this biphasic response were blocked by
yohimbine, a selective -AR antagonist. Preincubation
of myometrial membranes with G and/or G
antisera eliminated
-AR mediated attenuation or
potentiation of isoproterenol-stimulated adenylyl cyclase, thus
indicating that both the inhibitory and stimulatory components are
mediated via G and G
. In addition, type II
and IV adenylyl cyclases were identified by Northern blotting in the
pregnant rat myometrium. Altogether these data strongly suggest that
the
-AR at mid-pregnancy potentiates adenylyl cyclase
types II and IV through
released from G
and
G
proteins, whereas the
-AR expression
at term may be related to persistent inhibition.
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