Discrimination by dipyridamole of two types of responses to adenosine and ATP of the carbachol-induced contraction of guinea-pig trachea.

Two types of effect of purines on the carbachol-induced contraction of the guinea-pig trachea in the presence or absence of glucose were evaluated using dipyridamole, and adenosine uptake inhibitor. ATP exerted a greater relaxant effect on the carbachol (10(-6) M)-induced contraction than did adenosine in concentrations ranging from 10(-4) to 10(-3) M. These effects of purines were enhanced by pretreatment with dipyridamole (10(-5) M) but were virtually unaffected by the purine receptor antagonists theophylline (10(-5) M) and quinidine (10(-5) M). The contraction evoked by carbachol was gradually reduced and was almost abolished 4-5 h after exposure to the glucose-free solution. This reduction was almost eliminated by readmitting glucose, and was restored to a certain degree by introducing ATP or adenosine. ATP was less effective than adenosine. This effect of purines but not that of glucose, was markedly diminished by pretreatment with dipyridamole (3 X 10(-6) M to 10(-5) M). The restoration of the carbachol-induced contraction following introduction of purines or glucose was completely antagonized by atropine (10(-6) M). These results suggest that the extracellular effects of adenosine and ATP on the carbachol-induced contraction in normal solution are potentiated by dipyridamole, whereas the possible intracellular effects of these purines in the glucose-free solution are inhibited by this adenosine uptake inhibitor.