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Adenosine-Regulated Cell Proliferation in Pituitary Folliculostellate and Endocrine Cells: Differential Roles for the A₁ and A_2B Adenosine Receptors

Departments of Medicine and Pathology (P.J.S.), University of Wales College of Medicine, Cardiff, United Kingdom CF14 4XN

Address all correspondence and requests for reprints to: Dr. D. A. Rees, Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom CF14 4XN. E-mail: . reesda{at}cf.ac.uk

A₁ and A₂ adenosine receptors have been identified in the pituitary gland, but the cell type(s) on which they are located and their effects on pituitary cell growth are not known. Therefore, we analyzed the expression of A₁ and A₂ receptors in primary rat anterior pituitary cells, two pituitary folliculostellate (TtT/GF and Tpit/F1) and two pituitary endocrine (GH₃ and AtT20) cell lines, and compared their effects on cell proliferation. In anterior pituitary and folliculostellate cells, adenosine and adenosine receptor agonists (5'-N-ethylcarboxamidoadenosine, a universal agonist, and CGS 21680, an A_2A receptor agonist) stimulated cAMP levels with a rank order of potency that indicates the presence of functional A_2B receptors. This stimulation, however, was not observed in either GH₃ or AtT20 cells, where adenosine and the A₁ receptor agonist 2-chloro-N⁶-cyclopentyladenosine inhibited VIP/forskolin-stimulated cAMP production. Expression of A_2B and A₁ receptors in the folliculostellate cells and that of the A₁ receptor in the endocrine cells were confirmed by RT-PCR, immunocytochemistry, and ligand binding. Adenosine and 5'-N-ethylcarboxamidoadenosine dose-dependently (10 nM to 10 µM) stimulated growth in the folliculostellate, but not in the endocrine, cells, whereas in the latter, 100 µM adenosine and 2-chloro-N⁶-cyclopentyladenosine inhibited cell proliferation by slowing cell cycle progression. These data highlight the differential expression of A₁ and A_2B adenosine receptors in pituitary cells and provide evidence for opposing effects of adenosine on pituitary folliculostellate and endocrine cell growth.

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