Expression of G-protein-coupled receptor kinases in pregnant term and non-pregnant human myometrium.
There is evidence for hormonal receptor desensitisation in human myometrium, but little is known about the mechanisms involved in the loss of myometrial response to agonists such as beta(2)-adrenergic agonists, prostaglandin gamma and oxytocin. It is well known that the receptors for these hormones are coupled to G-proteins. The first step of receptor desensitisation is the phosphorylation of activated receptors by a G-protein-coupled receptor kinase (GRK). GRKs are members of a multigene family and the various subtypes differ in their localisation, regulation and mode of action. We have used Western blotting and reverse transcription PCR to identify the GRKs present in human myometrium from pregnant and non-pregnant women as well as in cultured human myometrial cells. We have found that human myometrium expresses the GRK subtypes 2, 4gamma, 5 and 6. On the other hand, GRK3 and the isoforms GRK4alpha, beta and delta were not found in myometrial tissue. Our data indicate that GRK2 is only expressed in pregnant term myometrium and is not found in non-pregnant tissue. Moreover, GRK6 appears to be expressed at a much higher level in pregnant term tissue than in non-pregnant myometrium. Our observations suggest that GRK2 and GRK6 may contribute to the regulation of uterine contractility at term. Further work is necessary to determine whether GRKs and receptor desensitisation play a role in disorders of uterine contractility.
Brenninkmeijer
C B
CB
University of Oxford, Nuffield Department of Obstetrics and Gynaecology, Women's Centre, Oxford OX3 9DU, UK.
Price
S A
SA
López Bernal
A
A
Phaneuf
S
S
D015153:Blotting, Western; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis*; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2; D054771:G-Protein-Coupled Receptor Kinase 4; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases; D006801:Humans; D009215:Myometrium / Q000201:enzymology*; D011247:Pregnancy / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014590:Uterine Contraction / Q000502:physiology*; D051552:beta-Adrenergic Receptor Kinases
D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C496567:GRK2 protein, human; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; 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; C517855:GRK4 protein, human; C517898:GRK5 protein, human