Modification of transmitter release from periarterial nerve terminals by dipyridamole in canine isolated splenic artery.
1. The aim of the present study was to determine the modulatory effects of dipyridamole on purinergic and adrenergic transmission in the canine isolated, perfused splenic artery. 2. Periarterial nerve electrical stimulation readily induced a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X receptor-mediated constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated response. 3. Exposure of tissues to dipyridamole (0.1-1 micro mol/L) dose-dependently inhibited both the first and second peaks of the vasoconstrictor response at a low frequency of stimulation (1 Hz), whereas at an intermediate frequency of stimulation (4 Hz), the first peak of the response was depressed without any significant effect being observed on the second peak of constriction. 4. At a higher dose (1 micro mol/L) dipyridamole potentiated vasoconstrictor responses to noradrenaline (0.03-1 nmol). At any doses used, dipyridamole had no effect on the vasoconstrictor responses to ATP (0.03-1 micro mol). 5. Tyramine (0.01-0.3 micro mol) induced vasoconstriction in a dose-dependent manner. The dose-response curves for tyramine were shifted to the right following treatment with dipyridamole (0.1-1 micro mol/L). 6. The present results indicate that dipyridamole may inhibit purinergic and adrenergic transmission presynaptically, whereas postsynaptically dipyridamole may potentiate the adrenergic vascular constriction by inhibition of transmitter uptake.
Department of Molecular Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Makoto
M
Naito
Xiao-Ping
XP
Yang
Shigetoshi
S
Chiba
D000255:Adenosine Triphosphate / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013157:Splenic Artery / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009435:Synaptic Transmission; D014439:Tyramine / Q000008:administration & dosage / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D018048:Receptors, Purinergic P2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D009638:Norepinephrine; D014439:Tyramine