Modulation of alpha 2-adrenergic receptors of rat vas deferens by adenosine receptors.

The effects of adenosine and its derivatives on binding of alpha 2-adrenergic receptor ligands with homogenates of rat vas deferens were examined. Adenosine and 2-chloradenosine increased the amount of [3H]clonidine binding. ATP had a slight effect, but AMP and adenine had none. The effect of adenosine was inhibited by theophylline. On the other hand, [3H]yohimbine binding was not influenced by 2-chloradenosine. The inhibitory effect of clonidine on [3H]yohimbine binding was strengthened by 2-chloradenosine, indicating an increase in affinity of alpha 2-adrenergic receptors for clonidine. Similar results were obtained with intact rat vas deferens pretreated with 2-chloradenosine. Then, it was found that presynaptic inhibition of noradrenaline release by clonidine was increased by pretreatment with 2-chloradenosine as judged by the contractile response of vas deferens induced by electrical stimulation. From these results it was concluded that adenosine and its derivatives cause a configurational change in presynaptic alpha 2-adrenergic receptors through activation of adenosine receptors. The induced configuration of alpha 2-receptors with high affinity for agonists seemed to be that of the active functional state, because the inhibitory effect of clonidine on norepinephrine release was potentiated by pretreatment with 2-chloradenosine.