The effects of dopamine receptor and α‐adrenoceptor agonists and antagonists on the stimulation‐evoked overflow of radioactivity from strips of dog saphenous vein previously loaded with [3H]‐noradrenaline have been examined alone and in combination. In the presence of neuronal and extraneuronal catecholamine uptake inhibitors, noradrenaline (0.1–1 × 10−6 m) and dopamine (0.01–1 × 10−6 m) both inhibited the stimulation‐evoked overflow of radioactivity. Sulpiride (1 × 10−6 m) was without effect and prazosin (1 × 10−7 m) had little effect on stimulation‐evoked overflow but yohimbine enhanced it approximately 2 fold; the effect of yohimbine was similar at concentrations of 1 × 10−7 and 1 × 10−6 m. Sulpiride abolished the inhibitory effect of dopamine on stimulation‐evoked overflow, but was without effect against noradrenaline. When allowance was made for the effects of yohimbine, alone, on overflow, yohimbine (1 × 10−7 m) had no effect against dopamine and minimal effects against noradrenaline. A similar result was obtained when the concentration of yohimbine was increased to 1 × 10−6 m. Prazosin did not antagonize the effect of noradrenaline. In the absence of the uptake inhibitors, clonidine (0.01–1 × 10−5 m) inhibited stimulation‐evoked overflow of radioactivity. Yohimbine (1 × 10−6 m) was without effect on its own and antagonized the effects of clonidine at a concentration of 0.1 × 10−5 m, but not at 0.01 or 1.0 × 10−5 m. These findings suggest that dopamine inhibits overflow by stimulating presynaptic dopamine receptors on the terminals of the noradrenergic nerves supplying the dog saphenous vein. The interaction between yohimbine and noradrenaline is discussed in terms of the current concepts of control of transmitter release mediated via presynaptic α2‐adrenoceptors.

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1 We have investigated the influence of chemical sympathectomy or bilateral adrenal demedullation on vasopressor responses produced by the alpha 1-adrenoreceptor agonist, phenylephrine, and the alpha 2-adrenoreceptor agonist, M-7, in pithed rats to see whether either procedure induced selective supersensitivity to either of these compounds. 5-HT, a tryptaminergic vasopressor agent, was also used to discriminate between nonspecific change in vascular responsiveness and those mediated via alpha-adrenoreceptors. 2 Adrenal demedullation caused a slight reduction in the sensitivity to all agonists. Chemical sympathectomy significantly reduced the vasopressor responses to all doses of phenylephrine, but responses to 5-HT were unchanged. In contrast there was a tendency for responses to M-7 to be greater in sympathectomized rats than in untreated rats. 3 It is concluded that circulating adrenal medullary catecholamines do not physiologically modulate vascular alpha-adrenoreceptor function. The differential effect of chemical sympathectomy on the vasopressor responses to phenylephrine and M-7 might be explained in terms of a small increase in the ratio of vascular alpha 2 : alpha 1-adrenoreceptors, that receive a noradrenergic innervation.

Taurine is an abundant amino acid found in mammalian tissues and it has been suggested to have cytoprotective functions. The aim of the present study was to determine if taurine had the potential to reduce oxidative stress associated with metal-stimulated catecholamine oxidation. Taurine and structural analogs of taurine were tested for their ability to inhibit metal-stimulated quinone formation from dopamine or L-dopa. Oxidative damage to proteins and lipids were also assessed in vitro and the effects of taurine were determined. Taurine (20 mM) was found to decrease significantly ferric iron (50-500 microM)- and manganese (10 microM)-stimulated L-dopa or dopamine oxidation. Taurine had no effect on zinc-induced dopamine oxidation and slightly potentiated copper- and NaIO(4)-stimulated quinone formation. Ferric iron-stimulated lipid peroxidation was not affected by taurine (1-20 mM). Protein carbonyl formation induced by ferric iron (500 microM) and L-dopa (500 microM) was significantly reduced by 10 mM taurine. The cytotoxicity of L-dopa (250 microM) and ferric chloride (75 microM) to LLC-PK(1) cells was attenuated by 10 mM taurine or hypotaurine. Homotaurine alone stimulated L-dopa oxidation and potentiated the cytotoxic effects of ferric iron. Homotaurine was found to be cytotoxic when combined with L-dopa or L-dopa/iron. In contrast, hypotaurine inhibited quinone formation and protected LLC-PK(1) cells. These studies suggest that taurine may exhibit cytoprotective effects against the oxidation products of catecholamines by acting as a scavenger for free radicals and cytotoxic quinones.