| Abstrakt: |
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 α/β‐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).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 μMand fenoldopam acted like a partial agonist (pD2=8.31±0.09, α=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 μM), whereas it did not alter the effects of fenoldopam (pD2=8.40±0.09, α=0.68) and SKF 82958 (pD2=8.58±0.08).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.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.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. |
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