ADENOSINE A2 RECEPTOR-MEDIATED STIMULATION OF CYCLIC-AMP IN CULTURED CHICKEN PINEAL CELLS

The pineal gland of vertebrates produces the time-keeping hormone mela tonin in a rhythmic manner. Regulation of melatonin production is a mu ltifactorial process. In the chicken, light, perceived through the sku ll, and norepinephrine, acting through alpha 2-adrenergic receptors, s ynergistically inhibit day time melatonin production. In addition, ade nosine exerts autocrine/paracrine modulatory effects on melatonin secr etion. In an attempt to elucidate how these effects of adenosine are m ediated, chicken pineal cells were cultured, in the dark during day ti me, in the presence of different analogs of adenosine. When the adenos ine transmembranous carrier was inhibited, chloroadenosine stimulated cyclic AMP (cAMP) accumulation in a time- and dose-dependent manner. T he effects were antagonized by 8-phenyltheophylline, an antagonist at the A1/A2 adenosine receptors. A dose-dependent stimulation of cAMP ac cumulation was also obtained with other adenosine agonists, with the f ollowing order of potency: N-ethylcarboxamidoadenosine > cyclopentylad enosine > R-phenyl-isopropyladenosine. The stimulatory effect of the l atter compound was still observed when basal cAMP levels were increase d in the presence of forskolin. Under our experimental conditions no i nhibition of cAMP content was observed. Our results are consistent wit h the idea that stimulation of melatonin secretion by adenosine analog s is mediated through A2 receptors.