Adenosine A2 receptor-mediated stimulation of cyclic AMP in cultured chicken pineal cells

The pineal gland of vertebrates produces the time-keeping hormone melatonin in a rhythmic manner. Regulation of melatonin production is a multifactorial process. In the chicken, light, perceived through the skull, and norepinephrine, acting through alpha 2-adrenergic receptors, synergistically inhibit day time melatonin production. In addition, adenosine exerts autocrine/paracrine modulatory effects on melatonin secretion. In an attempt to elucidate how these effects of adenosine are mediated, chicken pineal cells were cultured, in the dark during day time, in the presence of different analogs of adenosine. When the adenosine transmembranous carrier was inhibited, chloroadenosine stimulated cyclic AMP (cAMP) accumulation in a time- and dose-dependent manner. The effects were antagonized by 8-phenyltheophylline, an antagonist at the A1/A2 adenosine receptors. A dose-dependent stimulation of cAMP accumulation was also obtained with other adenosine agonists, with the following order of potency: N-ethylcarboxamidoadenosine > cyclopentyladenosine > R-phenyl-isopropylade-nosine. The stimulatory effect of the latter compound was still observed when basal cAMP levels were increased in the presence of forskolin. Under our experimental conditions no inhibition of cAMP content was observed. Our results are consistent with the idea that stimulation of melatonin secretion by adenosine analogs is mediated through A2 receptors.