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Up regulation of ARFGEF PSCD3 expression in labour represents a mechanism for receptor desensitisation in human myometrium
  1. J Lartey1,
  2. K Venkateswarlu2,
  3. A López Bernal3
  1. 1Institute of Cellular Medicine, University of Newcastle, Newcastle, UK
  2. 2Institute of Life Science, University of Swansea, Swansea, UK
  3. 3Division of Obstetrics and Gynaecology, University of Bristol, Bristol, UK


ADP ribosylation factors ARF1 and ARF6 are monomeric GTP binding proteins that regulate desensitisation of G protein coupled receptor (GPCRs) like the luteinizing hormone (LH) and oxytocin receptor.1,2 ARF GTPases are activated an ARF guanine nucleotide exchange factor ARFGEF called pleckstrin homology, Sec7 and coiled-coil domains 3 (PSCD3) formerly known as ARNO. Activated LHRH binds to β-arrestin, PSCD3 and inactive GDP bound ARF6. PSCD3 catalyses nucleotide exchange on ARF6 allowing the receptor to internalise. PSCD3 binds to membrane bound β-arrestin and frees it bind to GPCRs to induce receptor desensitisation.3

Aims and methods We postulate that ARF6 and PSCD3 interact with β-arrestin to regulate oxytocin receptor desensitisation in human myometrium. We used immunoblotting and immunohistochemistry to determine the relative expression and localisation of ARF6 and PSCD3 in non-pregnant and pregnant not in labour and labouring myometrial tissue homogenates.

Results We found a marked up regulation of PSCD3 expression in spontaneous labour group relative to non-pregnant and not in labour groups (p<0.05). ARF6 expression was invariant in all the groups examined (p>0.05). ARF6 and PSCD3 localised to myometrial fibres in tissue sections. The elevated expression of PSCD3 in labouring myometrium may represent a mechanism of receptor desensitisation during parturition.

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