Ontogeny of Catecholamine and Adenosine Receptor-Mediated cAMP Signaling of Embryonic Red Blood Cells: Role of cGMP-Inhibited Phosphodiesterase 3 and Hemoglobin

Author:

Baumann Rosemarie1,Blass Christian1,Götz Robert1,Dragon Stefanie1

Affiliation:

1. From the Physiologisches Institut, Universität Regensburg, Regensburg, Germany.

Abstract

Abstract We have previously shown that the cAMP signaling pathway controls major aspects of embryonic red blood cell (RBC) function in avian embryos (Glombitza et al, Am J Physiol 271:R973, 1996; and Dragon et al, Am J Physiol 271:R982, 1996) that are important for adaptation of the RBC gas transport properties to the progressive hypercapnia and hypoxia of later stages of avian embryonic development. Data about the ontogeny of receptor-mediated cAMP signaling are lacking. We have analyzed the response of primitive and definitive chick embryo RBC harvested from day 3 to 18 of development towards forskolin, β-adrenergic, and A2 receptor agonists. The results show a strong response of immature definitive and primitive RBC to adenosine A2 and β-adrenergic receptor agonists, which is drastically reduced in the last stage of development, coincident with the appearance of mature, transcriptionally inactive RBC. Modulation of cGMP-inhibited phosphodiesterase 3 (PDE3) has a controlling influence on cAMP accumulation in definitive RBC. Under physiological conditions, PDE3 is inhibited due to activation of soluble guanylyl cyclase (sGC). Inhibition of sGC with the specific inhibitor ODQ decreases receptor-mediated stimulation of cAMP production; this effect is reversed by the PDE3 inhibitor milrinone. sGC is acitivated by nitric oxide (NO), but we found no evidence for production of NO by erythrocyte NO-synthase. However, embryonic hemoglobin releases NO in an oxygen-linked manner that may activate guanylyl cyclase.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference19 articles.

1. Adenosine causes cAMP dependent activation of red cell carbonic anhydrase and 2,3BPG synthesis.;Glombitza;Am J Physiol,1996

2. Norepinephrine-mediated hypoxic stimulation of red cell embryonic carbonic anhydrase and 2,3BPG synthesis.;Dragon;Am J Physiol,1996

3. Adenosine 3′-5′-cyclic monophosphate (cAMP)-inducible pyrimidine 5′-nucleotidase and pyrimidine nucleotide metabolism of chick embryonic erythrocytes.;Dragon;Blood,1998

4. Oxygen and CO2 exchange and acid-base regulation in the avian embryo.;Tazawa;Am Zool,1980

5. The erythroid cells and haemoglobin of the chick embryo.;Bruns;Phil Trans R Soc Lond B,1973

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