Effect of adenosine analogues on plasma corticosterone concentration in rats.

In this study we examined the effect of the adenosine analogues: N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine and 5'-N-ethylcarboxamidoadenosine on the plasma corticosterone concentration in rats. It was found that N6-cyclohexyladenosine (0.1-3.0 mg/kg), L-N6-phenylisopropyladenosine (0.1-1.0 mg/kg) and 5'-N-ethylcarboxamidoadenosine (0.01-1.0 mg/kg) dose-dependently increased the plasma corticosterone level. The effects of N6-cyclohexyladenosine (0.1 mg/kg) and L-N6-phenylisopropyladenosine (0.1 mg/kg) were completely blocked in animals pretreated with dexamethasone (3 x 1 mg/kg), as well as in animals with a pharmacological blockade of the release of hypothalamic corticotropin-releasing factor induced by chloropromazine (10 mg/kg), morphine (20 mg/kg) and nembutal (25 mg/kg), whereas the corticosterone response to 5'-N-ethylcarboxamidoadenosine (0.01 mg/kg) was blocked in dexamethasone-pretreated rats only. On the other hand, the adenosine receptor antagonists: 8-(p-sulfophenyl)-theophylline (30 mg/kg), 8-phenyltheophylline (10 and 30 mg/kg), 1,3-dipropyl-8-(2-amino-4-chloro)-phenylxanthine (1 and 3 mg/kg) and 1,3-dipropyl-7-methylxanthine (1 mg/kg) did not affect the corticosterone response to N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine or 5'-N-ethylcarboxamidoadenosine. The obtained results indicate that N6-cyclohexyladenosine and L-N6-phenylisopropyladenosine stimulate the corticosterone secretion at the hypothalamic level, whereas 5'-N-ethylcarboxamidoadenosine is likely to act at the pituitary level. Although the effects produced by the adenosine analogues show that both A1 and A2 receptors are involved in the corticosterone response, negative results of the interaction studies with adenosine receptor antagonists indicate that further experiments are necessary to elucidate this problem.