ACTIONS OF DIPYRIDAMOLE ON ENDOGENOUS AND EXOGENOUS NORADRENALINE IN THE DOG MESENTERIC VEIN

1 In the isolated mesenteric vein of the dog, dipyridamole inhibited both the excitatory junction potential (e.j.p.) and the slow depolarization evoked by perivascular nerve stimulation, to 60-70% of control, with no change in the postjunctional membrane potential. These inhibitory actions of dipyridamole were not modified by 8-phenyltheophylline or phentolamine, suggesting that the inhibition did not involve either the actions of endogenous adenosine or the prejunctional alpha-autoregulation mechanism. 2 Dipyridamole did not produce any detectable effects on either the postjunctional membrane depolarization produced by exogenously applied noradrenaline (NA). 3 Dipyridamole reduced the outflow of both the NA and the 3,4-dihydroxyphenylglycol (DOPEG) evoked by perivascular nerve stimulation to below 10% of control, the effect being much greater than that of exogenously applied adenosine (to about 90% of the control). 4 Exogenously-added NA was degraded by incubation with a segment of the vein. Dipyridamole itself produced degradation of NA and accelerated the NA-induced degradation. By contrast, pyrogallol, but not pargyline or imipramine, prevented the NA-induced degradation. 5 It is suggested that dipyridamole degrades NA directly, and also indirectly through activation of catechol-O-methyl transferase, with no alteration of the activity of monoamine oxidase or of the uptake mechanisms of NA into nerve terminals.