High level of alpha2-adrenoceptor in rat foetal liver and placenta is due to alpha2B-subtype expression in haematopoietic cells of the erythrocyte lineage.
1. Rat foetal liver contains large amounts of alpha2-adrenoceptors. The present work aimed to identify the receptor subtype and the cell type accounting for high expression and to clarify the mechanisms responsible for the sharp decrease in hepatic receptivity occurring during the late stage of foetal 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 (35.2+/-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 binding matched the pharmacological profile of the alpha2B-adrenoceptor and exclusively RNG transcripts were detected by RNase protection assays. 3. Isolation of cell fractions from foetal liver showed that alpha2B-adrenoceptor is primarily expressed by haematopoietic cells. Consistent with this view, the receptor is found to be abundant in foetal blood, carried by reticulocytes. The expression in blood gradually declines to zero at 3 weeks of age and it is not recovered following induction of reticulocytosis in adults. 4. In foetal reticulocytes, a low proportion of the receptor population is coupled to G-protein. The alpha2-agonist UK14304 has a marginal effect on cyclic AMP level but significantly increases arachidonic acid release. The function of the receptor remains to be elucidated. However, together with observations on alpha2B-knockout mice, the current finding strongly suggests a role for alpha2B-adrenoceptor during foetal haematopoiesis in rodents.
Cussac
D
D
INSERM U388, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse Cedex 4, France.
Schaak
S
S
Denis
C
C
Flordellis
C
C
Calise
D
D
Paris
H
H
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000378:metabolism; D001667:Binding, Competitive; D019070:Cell Lineage; D000242:Cyclic AMP / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D008099:Liver / Q000196:embryology* / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism*; D017701:Reticulocyte Count; D013154:Spleen / Q000378:metabolism; D013379:Substrate Specificity
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D004921:Erythropoietin; D016718:Arachidonic Acid; D012313:RNA; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins