ISSN:
1432-1912
Keywords:
Dopamine
;
Vascular dopamine receptor
;
Rabbit mesenteric artery
;
Metoclopramide
;
Droperidol
;
Relaxation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary In the isolated rabbit mesenteric artery, pretreated with phenoxybenzamine (10−5 M) and contracted with prostaglandin F2α (5×10−7–5×10−6 M) the relaxing effects of dopamine were analyzed. 1. Dopamine (10−6–3×10−4 M) produced a concentration-dependent relaxation of the contracted arterial strips. The β-adrenoceptor antagonist pindolol (10−7M) did not alter this relaxation, but did significantly antagonize relaxations caused by isoprenaline (10−9–10−5 M). 2. The dopamine-receptor antagonists metoclopramide (2.5×10−5–10−4 M) and droperidol (3×10−6–3×10−5 M), on the other hand, significantly suppressed dopamine-induced relaxations in a dose-dependent manner. The pA2-values of metoclopramide and droperidol were 5.18 and 6.05, respectively. Metoclopramide (2.5×10−5–10−4 M) and droperidol (3×10−6 and 10−5 M) did not inhibit relaxations evoked by isoprenaline; only in concentrations above 10−5 M droperidol showed a β-adrenolytic side effect. 3. Metoclopramide (5×10−5 and 10−4 M) and droperidol (10−5 and 3×10−5 M) had no effect on adenosine-or papaverine-induced relaxations; thus, unspecific effects of the antagonists can be excluded. 4. The anticholinergic agent atropine (10−6 M) and the antihistaminic agent metiamide (10−5 M) did not modify dopamine-induced relaxations indicating that cholinergic and histaminergic mechanisms are not involved in the action of dopamine. In addition, stimulation of presynaptic receptors and/or indirect effects of dopamine via the release of endogenous noradrenaline do not play any role in the relaxing effects of dopamine, since on arteries derived from rabbits pretreated with 6-hydroxydopamine (3×30 mg/kg i.v.) dopamine-induced relaxations were very similar to those obtained on arteries from untreated rabbits. 5. It is concluded that on the isolated rabbit mesenteric artery dopamine produces its relaxing effect through direct stimulation of vascular dopamine receptors. These effects can be antagonized by metoclopramide and droperidol. Thus, the present results support the view that dopamine receptors exits on vascular smooth muscle mediating vasodilation. 6. Studies on structure-activity relationships demonstrate that the 3,4-dihydroxy substitution at the benzene ring of the phenylethylamine molecule is essential for stimulation of the vascular dopamine receptor: Epinine, SK & F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine) and apomorphine, which contain this structure, were found to be active at the receptor. 3-(2-Dipropylamino-ethyl)phenol, lacking in the 4-OH-group, and 3-methoxytyramine, where the 3-OH-group is methylated, on the other hand, were found to be inactive.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00507222
