Effects of adenosine compounds on the contractile response of isolated canine blood vessels to various agonists

Effects of adenine and adenosine compounds (adenosine, AMP, ATP, cyclic AMP and dibutyryl cyclic AMP) on the contractile responses of helically cut strips of canine superior mesenteric arteries to various agonists (K+, norepinephrine, angiotensin II and Ba2+), to transmural electrical stimulation and on Ca2+-contractures of K+-depolarized strips were studied. The contractions induced by these agonists were suppressed, dose dependently, but to a different degree by these adenosine compounds, with the exception of the potentiating action of ATP on the Ba2+-induced contraction. The suppression of the effect of norepinephrine, angiotensin II and transmural stimulation was appreciably greater than that of K+ and Ba2+. Adenine was equally or more effective in inhibiting the contractions induced by these agonists than were the other adenosine compounds used. The order of relative inhibitory potency was adenine ≥ adenosine ≥ AMP = ATP>cyclic AMP = dibutyryl cyclic AMP. The ATP-induced contraction was influenced in a different manner by each adenosine compound. Adenosine and cyclic AMP did not affect the ATP-induced contraction but AMP and dibutyryl cyclic AMP in a narrow range of concentrations enhanced the contraction. On the contrary, adenine and ATP inhibited the ATP contraction, dose-dependently, resulting in tachyphylaxis, with the repeated application of ATP. The present results suggest that adenine moiety in the molecule plays an important role in the inhibitory action of adenosine compounds, and that the antagonistic action of adenosine compounds is due to their inhibitory actions on Ca2+-influx and Ca2+-release from cell stores.