Pharmacological evidence for the presence of a peripheral postjunctional D2-like dopamine receptor in rabbit splenic artery.
1. This study was designed to investigate the involvement of postjunctional D2-like receptors in a rabbit vasculature model used to evaluate the D1-like agonist activity. Dopamine, epinine and (-)-DP-5,6-ADTN, three mixed D1/D2-like agonists, fenoldopam and SKF 82958, two selective D1-like agonists and SKF 89124, a selective D2-like agonist, were administered cumulatively in precontracted and alpha/beta-blocked rabbit splenic artery rings in order to evaluate their D1-like-mediated vasorelaxant activity before and after pretreatment with the selective D2-like antagonist YM 09151-2 (1 nM). 2. Dopamine (pD2=6.35+/-0.09), epinine (pD2=6.73+/-0.13), (-)-DP-5,6-ADTN (pD2=7.56+/-0.09) and SKF 82958 (pD2=8.55+/-0.10) reversed completely the U46619-induced contracture whereas SKF 89124 was inactive up to 10 microM and fenoldopam acted like a partial agonist (pD2=8.31+/-0.09, alpha=0.62). The selective D2-like dopamine receptor antagonist YM 09151-2 (1 nM) significantly (P<0.05) potentiated the vasorelaxant activity of dopamine (pD2=7.01+/-0.07), epinine (pD2=7.14+/-0.08), (-)-DP-5,6-ADTN (pD2=8.19+/-0.09) and SKF 89124 (40% relaxation at 10 microM), whereas it did not alter the effects of fenoldopam (pD2=8.40+/-0.09, alpha=0.68) and SKF 82958 (pD2=8.58+/-0.08). 3. The D2-like antagonist YM 09151-2 induced the same degree of effect with all the substances tested in both endothelium-denuded and endothelium-intact preparations. 4. The selective D2-like dopamine receptor agonist SKF 89124 did not produce any intrinsic effect on the splenic artery, but was able to produce a rightward shift of the forskolin-induced relaxation. 5. The results of these experiments support the existence of a non-endothelial postjunctional D2-like dopamine receptor counteracting the D1-like-mediated vasodilatation in rabbit splenic artery, probably by the inhibition of adenylate cyclase.
Zanzottera
D
D
Zambon Group S.p.A., R&D Division, Bresso (Milan), Italy.
Ferlenga
P
P
Marchini
F
F
Semeraro
C
C
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009451:Neuroeffector Junction / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013157:Splenic Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2