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Concomitant Increase of G Protein-Coupled Receptor Kinase Activity and Uncoupling of ß-Adrenergic Receptors in Rat Myometrium at Parturition

Laboratoire de Physiologie de la Reproduction, ESA Centre National de la Recherche Scientifique 7080, Université Pierre et Marie Curie, 75252 Paris CEDEX 05, France

Address all correspondence and requests for reprints to: Joëlle Cohen-Tannoudji, Laboratoire de Physiologie de la Reproduction, ESA Centre National de la Recherche Scientifique 7080, Université Pierre et Marie Curie, 4 Place Jussieu, 75252 Paris CEDEX 05, France. E-mail: jtannoud{at}snv.jussieu.fr

The myometrial ß-adrenergic receptor (ß-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 ß-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 ß-AR and adenylyl cyclase and may thus contribute to the initiation of myometrial contractions at term.

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