Summary
The contractile effects of dopamine and noradrenaline were compared in the rat isolated vas deferens, in order to obtain evidence for the presence or absence of postsynaptic dopamine receptors in this tissue. Attention was given to the role of several factors known to interfere with receptor characterization.
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1.
The preparation presented a slight tachyphylaxis for dopamine and a loss of sensitivity to that agonist after treatment with reserpine. These effects were not observed for noradrenaline.
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2.
Cocaine potentiated the effects of noradrenaline and dopamine by 38.9 and 2.1 times respectively. Metanephrine induced a potentiation of 2.2 times for noradrenaline and did not significantly alter dopamine effects. These results indicate that dopamine is practically not taken up by neuronal or extraneuronal mechanisms. Noradrenaline is only slightly affected by extraneuronal uptake and greatly affected by neuronal uptake as previously shown.
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3.
The competitive antagonism of haloperidol, analyzed by means of Schild plots, and expressed through pA2 values, was similar for noradrenaline and dopamine when studied after blockade of neuronal uptake by cocaine. In the absence of cocaine, pA2 values for haloperidol were significantly lower when determined against noradrenaline than against dopamine.
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4.
The α-adrenoceptor antagonist yohimbine induced effects which were similar to those of haloperidol.
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5.
Pimozide and apomorphine induced a non-competitive-like antagonism towards both agonists similar to that induced by papaverine. This antagonism was added to a slight competitive inhibition.
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6.
It was not possible to differentiate the effects of noradrenaline and dopamine by means of protection experiments against irreversible blockade by phenoxybenzamine.
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7.
Potentiation of the maximal effects of noradrenaline, previously reported for several α-adrenoceptor antagonists, was also induced by haloperidol and low doses of apomorphine. This phenomenon was never observed when dopamine was used instead of noradrenaline, whichever the antagonist.
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8.
Our results provide evidence that differences observed among the effects of dopamine and noradrenaline are mostly due to differences on sensitivity towards neuronal uptake and to other minor factors. When the influence of these factors is taken into account, or avoided, the contractile effects for dopamine and noradrenaline are similar, indicating an interaction of both substances with a single type of postsynaptic α-adrenoceptor, in the rat vas deferens.
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Langeloh, A., Jurkiewicz, A. Analysis of the effects of dopamine and noradrenaline in relation to the proposed postsynaptic dopamine receptor in rat vas deferens. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 202–209 (1982). https://doi.org/10.1007/BF00500481
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DOI: https://doi.org/10.1007/BF00500481