Prolactin and cyclosporine modulate adenosine transporters and adenosine A1 receptors in the rat brain

Abstract

The existence of adenosine A1 receptors and adenosine transporters in the central nervous system has been well demonstrated, although their possible modulation by hormones and/or exogenous drugs is poorly understood. To further analyze these modulatory mechanisms, the effects of prolactin and cyclosporine (CyA) on adenosine A1 receptors and transporters were analyzed in the central nervous system. For this purpose the number and affinity of adenosine A1 receptors were measured using the specific antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and the transporters with the high affinity ligand nitrobenzylthioinosine (NBTI). This procedure was carried out in hyperprolactinemic and control male rats treated with CyA or its vehicle for 8 days. As expected, pituitary grafting increased plasma prolactin levels (p<0.01). CyA treatment reduced but did not normalize (p<0.05) this parameter in hyperprolactinemic rats and did not modify circulating prolactin in control animals. Both hyperprolactinemia and CyA treatment reduced the number of adenosine transporters by 70% and by 40% the number of A1 receptors. The Kd for transporters was also reduced in all experimental groups. Hyperprolactinemia increased the affinity of A1 receptors (p<0.01) and CyA treatment did not further modify this parameter. These data demonstrated that prolactin and CyA influence adenosine transporters and A1 receptors at the central nervous system and suggest the existence of an interaction between prolactin and CyA may be operating to modulate these processes.

Cyclosporin and tacrolimus increase plasma levels of adenosine in kidney transplanted patients

“…Previous studies showed that CsA and FK506 produce an increase in ADO levels by inhibition of the enzyme AK associated to the plasma membrane, in different cell types [10,11]. Moreover, an inhibition of cell uptake of the nucleoside has been described, and CsA has been shown to reduce by 67% the number of ADO transmembrane transporters in rat brain [20]. The mechanisms are closely related, as it has been demonstrated that it is unlikely that AK blocking may take place without the inhibition of cell uptake of ADO [33,34].…”

“…As a consequence, AK‐mediated ADO dephosphorylation to adenosine monophosphate (AMP) is inhibited, and cell release of ADO is promoted [9–11]. Moreover, an inhibition of ADO cell uptake has also been reported, and CsA has been described to reduce by 67% the number of ADO transporters in the rat brain [20]. The activity of CsA and FK506 on the ADO system was studied in vitro in red blood cells [9], endothelial cells [10] and T lymphocytes [11].…”