Antagonism by clonidine of the adenosine-induced inhibition of the twitch contraction of the guinea-pig Oddi sphincter.

The effects of clonidine on the purinergic inhibition of cholinergic transmission were investigated; we used the twitch contraction of a circular segment of the guinea-pig Oddi sphincter stimulated electrically. A circular segment of Oddi sphincter was contracted in a frequency-dependent manner by transmural nerve stimulation. Adenosine (10(-6) to 10(-4] produced a reduction of approximately 40% in the twitch contraction elicited at 5 Hz. The inhibition was antagonized by theophylline (10(-5) M), 8-phenyltheophylline (10(-6) M) or clonidine (10(-6) to 3 X 10(-6) M) but was enhanced by dipyridamole (3 X 10(-6) M). This antagonism produced by clonidine (3 X 10(-6) M) was almost unaffected by yohimbine (3 X 10(-6) M). The twitch contraction was also suppressed by N6-substituted adenosine analogs, L-PIA and CHA. The suppression was counteracted by theophylline or clonidine. The contraction produced by exogenously administered acetylcholine was not affected by clonidine and/or adenosine at all. The results suggest that clonidine, like theophylline, seems to exert these antagonistic effects by acting on the neuronal adenosine receptors in the guinea-pig Oddi sphincter muscle.