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

Prolactina y ciclosporina modulan los transportadores y receptores A1 de adenosina en cerebro de rata

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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.

Resumen

Es conocida la presencia transportadores y receptores de adenosina A1 en el sistema nervioso central, aunque su modulación por hormonas y/o drogas exógenas no está bien comprendida. Para contribuir a la comprensión de estos mecanismos moduladores, se analizan los efectos de la prolactina y ciclosporina A (CyA) sobre los receptores A1 y los transportadores de adenosina en el sistema nervioso central de rata. Para este propósito, se miden el número y la afinidad de los sitios de unión de la adenosina para los receptores A1, usando el antagonista específico 1,3-dipropil 8-ciclopentilxantina (DPCPX) y los transportadores con el ligando de alta afinidad nitrobenziltioinosina (NBTI). Este procedimiento se lleva a cabo en ratas macho control e hiperprolactinémicas tratadas con CyA o su vehículo durante 8 días. Como era de esperar, el implante hipofisario incrementa los niveles de prolactina plasmática (p<0.01). El tratamiento con CyA reduce pero no normaliza (p<0.05) este parámetro en ratas hiperprolactinémicas y no modifica la prolactina circulante en los animales control. La hiperprolactinemia y el tratamiento con CyA reducen el número de transportadores de adenosina en un 70% y el número de receptores en un 40%. También disminuye la Kd para los transportadores en todos los grupos experimentales. La hiperprolactinemia incrementa la afinidad de los receptores A1 (p<0.01) mientras que la CyA no modifica este parámetro. Estos datos demuestran que la prolactina y la CyA influyen sobre los transportadores y receptores A1 de adenosina en el sistema nervioso central y sugieren que podrían interactuar en su modulación.

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Authors and Affiliations

  1. Departamento de Bioquímica y Biología Molecular IV, Facultad de Veterinaria Universidad Complutense de Madrid, Univ. Complutense, 28040, Madrid, Spain

    M. D. Fideu & M. T. Miras-Portugal

  2. Departmento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense de Madrid, Univ. Complutense, 28040, Madrid, Spain

    A. Arce & A. I. Esquifino

Authors
  1. M. D. Fideu
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  2. A. Arce
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  3. M. T. Miras-Portugal
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  4. A. I. Esquifino
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Correspondence to A. I. Esquifino.

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Fideu, M.D., Arce, A., Miras-Portugal, M.T. et al. Prolactin and cyclosporine modulate adenosine transporters and adenosine A1 receptors in the rat brain. J. Physiol. Biochem. 56, 83–90 (2000). https://doi.org/10.1007/BF03179903

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