Prolactin and cyclosporine modulate adenosine transporters and adenosine A1 receptors in the rat brain.
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.
Fideu
M D
MD
Departamentos de Bioquímica y Biología Molecular IV, Facultad de Veterinaria y III, Universidad Complutense de Madrid, Spain.
Arce
A
A
Miras-Portugal
M T
MT
Esquifino
A I
AI
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006966:Hyperprolactinemia / Q000139:chemically induced; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D033703:Nucleoside Transport Proteins; D010903:Pituitary Gland, Anterior / Q000637:transplantation; D011388:Prolactin / Q000097:blood / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014970:Xanthines / Q000378:metabolism / Q000494:pharmacology
D002352:Carrier Proteins; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D013868:Thioinosine; D016572:Cyclosporine; D011388:Prolactin; C051360:1,3-dipropyl-8-cyclopentylxanthine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine