High level of alpha 2-adrenoceptor in rat foetal liver and placenta is dueto alpha 2B-subtype expression in haematopoietic cells of the erythrocyte lineage

1 Rat foetal liver contains large amounts of alpha2-adrenoceptors. The pres ent work aimed to identify the receptor subtype and the cell type accountin g for high expression and to clarify the mechanisms responsible for the sha rp decrease in hepatic receptivity occurring during the late stage of foeta l development. 2 Binding experiments indicated that the density of alpha2-adrenoceptors in the foetal liver (embryonic day 18; 615 +/- 155 fmol mg(-1) of protein) is 18 fold higher than in newborn or adult (35.21 +/-4.3 fmol mg(-1)). A high amount of receptor is also found in the placenta (443 +/- 53 fmol mg(-1)). In both tissues, the rank order of antagonists to inhibit radioligand bind ing matched the pharmacological profile of the alpha 2B-adrenoceptor and ex clusively RNG transcripts were detected by RNase protection assays. 3 Isolation of cell fractions from foetal liver showed that alpha 2B-adreno ceptor is primarily expressed by haematopoietic cells. Consistent with this view, the receptor is found to be abundant in foetal blood. carried by ret iculocytes. The expression in blood gradually declines to zero at 3 weeks o f age and it is not recovered following induction of reticulocytosis in adu lts. 4 In foetal reticulocytes, a low proportion of the receptor population is c oupled to G-protein. The alpha2-agonist UK14304 has a marginal effect on cy clic AMP level but significantly increases arachidonic acid release. The fu nction of the receptor remains to be elucidated. However, together with obs ervations on alpha 2B-knockout mice, the current finding strongly suggests a role for alpha 2B-adrenoceptor during foetal haematopoiesis in rodents.