Endocrine Abstracts (2002) 3 OC47

A2B adenosine receptors mediate the adenosine-induced increase in cell growth and IL-6 expression in pituitary folliculostellate cells

DA Rees, MD Lewis, BM Lewis, MF Scanlon & J Ham

Department of Medicine, University of Wales College of Medicine, Cardiff, UK.

Coordinated interaction between the immune and neuroendocrine systems is of key importance in regulating the host's response to inflammation and anoxic stress. Adenosine, released under such conditions in high concentration, modulates a number of inflammatory processes and can regulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis. Although adenosine receptors (ARs) have been described in the pituitary gland, the distribution of the receptor subtypes (A1, A2A, A2B or A3) have not been defined. Accordingly, we have analysed the distribution of ARs in primary rat anterior pituitary (AP) cells, and pituitary endocrine and folliculostellate (FS) cell lines, and compared their effects on cell growth and IL-6 expression. In AP and FS cells, adenosine and AR agonists (NECA, a universal AR agonist, and CGS 21680, a selective A2AR agonist) stimulated cAMP production with a potency order (NECA>adenosine>CGS 21680) indicating the presence of functional A2B receptors. This stimulation was not observed in endocrine cells where adenosine and the selective A1R agonist CCPA inhibited forskolin stimulated cAMP production. Gene and protein expression for the A2BR and A1R in FS cells, and the A1R in endocrine cells was confirmed by RT-PCR, immunocytochemistry and ligand binding. Adenosine stimulated the growth of FS cells via the A2BR but in higher concentration inhibited cell growth in endocrine cells via the A1R. Adenosine and NECA stimulated IL-6 (up to 10- and 30-fold) and VEGF (up to 1.5- and 3-fold) production in FS but not in endocrine cells, effects that were reversible by dexamethasone. These data highlight the differential actions of adenosine in folliculostellate and endocrine cells mediated respectively via the A2B and A1 adenosine receptors. The effects on FS cell growth and IL-6 release support important paracrine and autocrine roles for adenosine in pituitary physiology and pathophysiology.

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