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

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.

Proteomic Analysis of Chicken Chorioallantoic Membrane (CAM) during Embryonic Development Provides Functional Insight

“…In contrast, the collection of blood samples at ED12 was technically challenging, as the embryo size is tiny, and the blood volume until ED12 is less than 100 μ L [ 45 , 46 ]. In addition, it has been shown that the plasma protein composition does not change during embryonic development; rather, the cellular composition and morphology vary at different stages of embryonic development [ 13 , 45 , 47 , 48 ]. The CAM main functions include eggshell solubilization, Ca 2+ and nutrient transport, gaseous exchange, and protection against pathogen invasion [ 14 ].…”

Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells

“…It should be added that it has been reported that the soluble adenyl cyclase (sGC)/cGMP pathway can also increase the cAMP content of cells by cross-talking between the cAMP and cGMP signaling pathways [79][80][81][82]. It was shown that cGMP probably inhibits the phosphodiesterase to reduce cAMP degradation and thereby increases the mitochondria cAMP content [83]. Nevertheless, the nature of the cAMP-mediated response uncoupled by melatonin and its metabolites remains a matter of speculation.…”

Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light

“…It has been reported that the NO activated sGC/cGMP pathway can also increase the cAMP content of cells by crosstalking between the cAMP and cGMP signaling pathways [149,152,153]. cGMP probably inhibits the phosphodiesterase to reduce cAMP degradation and thereby increases its concentration [154]. Therefore, the NO/sGC/cGMP/cAMP pathway also has the potential to increase melatonin synthesis in response to NIR.…”