Concomitant increase of G protein-coupled receptor kinase activity and uncoupling of beta-adrenergic receptors in rat myometrium at parturition.
The myometrial beta-adrenergic receptor (beta-AR)-adenylyl cyclase pathway is markedly desensitized at the end of pregnancy in the rat. We have investigated whether changes in the amount and/or the activity of G protein-coupled receptor kinase (GRK) occurred at the same period of pregnancy. Using Northern and Western blotting, we have identified GRK2, GRK5, GRK6, and a small amount of GRK3 in late pregnant rat myometrium. GRK activity, as measured by in vitro phosphorylation of rhodopsin, was detected in both cytosolic and plasma membrane fractions. Interestingly, in the 6-10 h preceding parturition, there was a substantial increase (+190%) of myometrial membrane-associated GRK activity. This was associated with an increase in membrane GRK2 immunoreactivity. Such alterations occurred concomitantly with uncoupling of beta-AR, as assessed by quantification of high-affinity binding receptors. These data suggest that GRK activity increase may be one of the mechanisms underlying alterations in the coupling between beta-AR and adenylyl cyclase and may thus contribute to the initiation of myometrial contractions at term.
Simon
V
V
Laboratoire de Physiologie de la Reproduction, ESA Centre National de la Recherche Scientifique 7080, Université Pierre et Marie Curie, 75252 Paris CEDEX 05, France.
Mhaouty-Kodja
S
S
Legrand
C
C
Cohen-Tannoudji
J
J
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis*; D005260:Female; D054770:G-Protein-Coupled Receptor Kinase 3; D054771:G-Protein-Coupled Receptor Kinase 4; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases; D007743:Labor, Obstetric / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D051552:beta-Adrenergic Receptor Kinases
D011943:Receptors, Adrenergic, beta; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D054770:G-Protein-Coupled Receptor Kinase 3; C517851:Grk3 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054771:G-Protein-Coupled Receptor Kinase 4; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6; C517854:Grk4 protein, rat; C517897:Grk5 protein, rat