Effect of adenosine analogues on plasma corticosterone concentration in rats

Abstract

In this study we examined the effect of the adenosine analogues: N 6 -cyclohexyladenosine, L-N 6 -phenylisopropyladenosine and 5′-N-ethylcarboxamidoadenosine on the plasma corticosterone concentration in rats. It was found that N 6 -cyclohexyladenosine (0.1–3.0 mg/kg), L-N 6 -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 N 6 -cyclohexyladenosine (0.1 mg/kg) and L-N 6 -phenylisopropyladenosine (0.1 mg/kg) were completely blocked in animals pretreated with dexamethasone (3 × 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 30mg/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 N 6 -cyclohexyladenosine, L-N 6 -phenylisopropyladenosine or 5′-N-ethylcarboxamidoadenosine. The obtained results indicate that N 6 -cyclohexyladenosine and L-N 6 -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 A 1 and A 2 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.