Pharmacological evidence for the presence of a peripheral postjunctional D₂‐like dopamine receptor in rabbit splenic artery

Abstract

1 This study was designed to investigate the involvement of postjunctional D 2 -like receptors in a rabbit vasculature model used to evaluate the D 1 -like agonist activity. Dopamine, epinine and (7)-DP-5,6-ADTN, three mixed D 1 /D 2 -like agonists, fenoldopam and SKF 82958, two selective D 1 -like agonists and SKF 89124, a selective D 2 -like agonist, were administered cumulatively in precontracted and a/b-blocked rabbit splenic artery rings in order to evaluate their D 1 -like-mediated vasorelaxant activity before and after pretreatment with the selective D 2 -like antagonist YM 09151-2 (1 nM). 2 Dopamine (pD 2 =6.35+0.09), epinine (pD 2 =6.73+0.13), (7)-DP-5,6-ADTN (pD 2 =7.56+0.09) and SKF 82958 (pD 2 =8.55+0.10) reversed completely the U46619-induced contracture whereas SKF 89124 was inactive up to 10 mM and fenoldopam acted like a partial agonist (pD 2 =8.31+0.09, a=0.62). The selective D 2 -like dopamine receptor antagonist YM 09151-2 (1 nM) signi®cantly (P50.05) potentiated the vasorelaxant activity of dopamine (pD 2 =7.01+0.07), epinine (pD 2 =7.14+0.08), (7)-DP-5,6-ADTN (pD 2 =8.19+0.09) and SKF 89124 (40% relaxation at 10 mM), whereas it did not alter the e ects of fenoldopam (pD 2 =8.40+0.09, a=0.68) and SKF 82958 (pD 2 =8.58+0.08). 3 The D 2 -like antagonist YM 09151-2 induced the same degree of e ect with all the substances tested in both endothelium-denuded and endothelium-intact preparations. 4 The selective D 2 -like dopamine receptor agonist SKF 89124 did not produce any intrinsic e ect 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 D 2 -like dopamine receptor counteracting the D 1 -like-mediated vasodilatation in rabbit splenic artery, probably by the inhibition of adenylate cyclase.

Cardiovascular responses to combined treatment with selective monoamine oxidase type B inhibitors and L‐DOPA in the rat

“…Dopamine activates both D1‐ and D2‐type receptors in the periphery. Agonist effects at D1‐type receptors cause vasodilatation by direct action at vascular smooth muscle cells; agonist effects at presynaptic D2‐type receptors cause vasodilatation indirectly, by reduction in release of noradrenaline, and agonist effects at post‐synaptic D2 receptors may reduce D1‐mediated vasodilatation by inhibition of adenylate cyclase (Goldberg and Kohli, 1983; Goldberg and Rajfer, 1985; Kobayashi et al ., 1994; Zanzottera et al ., 1998). In addition, dopamine displaces noradrenaline from neuronal storage sites (Henning and Rubenson, 1970; Dayan and Finberg, 2003).…”