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Pregnancy switches adrenergic signal transduction in rat and human uterine myocytes as probed by BK Ca channel activity
Author(s) -
Zhou XiaoBo,
Wang GeXin,
Hüneke Bernd,
Wieland Thomas,
Korth Michael
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.t01-1-00339.x
Subject(s) - isoprenaline , endocrinology , medicine , pertussis toxin , chemistry , g protein , myometrium , gs alpha subunit , iberiotoxin , myocyte , inhibitory postsynaptic potential , signal transduction , adenylyl cyclase , stimulation , potassium channel , biology , biochemistry , uterus
1 We used large conductance Ca 2+ ‐activated K + (BK Ca ) channel activity as a probe to characterize the inhibitory/stimulatory G protein (G i /G s ) signalling pathways in intact cells from pregnant (PM) and non‐pregnant (NPM) myometrium. 2 Isoprenaline (10 μM) enhanced the outward current ( I out ) in PM cells and inhibited I out in NPM cells. Additional application of the α 2 ‐adrenoceptor (α 2 ‐AR) agonist clonidine (10 μM) further enhanced the isoprenaline‐modulated I out in PM cells but partially antagonized I out in NPM cells. Clonidine alone did not affect I out . The specific cAMP kinase (PKA) inhibitor H‐89 (1 μM) abolished the effects of isoprenaline and clonidine. The specific BK Ca channel blocker iberiotoxin (0·1 μM) inhibited I out by ≈80 %; the residual current was insensitive to isoprenaline. 3 Inhibition of G i activity by either pertussis toxin or the GTPase activating protein RGS16 abolished inhibitory as well as stimulatory effects of clonidine on I out . 4 Transducin‐α, a scavenger of G i βγ dimers, converted the stimulatory action of clonidine on I out into an inhibitory effect. Free transducin‐βγ enhanced both the stimulatory and the inhibitory effects of isoprenaline on I out . 5 The results demonstrate that BK Ca channel activity is a sensitive probe to follow adenylyl cyclase‐cAMP‐PKA signalling in myometrial smooth muscle cells. Both G i α‐mediated inhibition and G i βγ‐mediated stimulation can occur in the same cell, irrespective of pregnancy. It is speculated that the coupling between α 2 ‐AR and G i proteins is more efficient during pregnancy and that G i βγ at high levels simply override the inhibitory action of G i α.