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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