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 facilitation process of the e.j.ps or 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.
Li
Y J
YJ
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Zhang
G L
GL
Suzuki
H
H
Kuriyama
H
H
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008839:Microelectrodes; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D002395:Catecholamines; D008734:Methoxyhydroxyphenylglycol; D004176:Dipyridamole; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D010646:Phentolamine