Dopamine and alpha adrenoceptor agonists inhibit neurotransmission in the cat spleen through different presynaptic receptors

In the perfused cat spleen labeled with [³H]norepinephrine, and in the presence of 29 μM cocaine, exposure to exogenous (-)-norepinephrine (0.01-1 μM), (-)-epinephrine (0.01-1 μM) or (-)-α-methylnorepinephrine (0.01-1 μM) produced a concentration dependent inhibition of ³H-transmitter released by nerve stimulation (1 Hz, during 5 min, 0.5 msec duration, supramaximal voltage). The three catecholamines increased the perfusion pressure through activation of postsynaptic alpha adrenoreceptors. Under similar experimental conditions 0.01 to 1 μM dopamine or apomorphine inhibited ³H-transmitter overflow induced by nerve stimulation and these effects were completely antagonized by 1 μM (S-R)-sulpiride, a dopamine receptor blocking agent, devoid of alpha adrenoceptor blocking properties. Neither dopamine nor apomorphine increased the perfusion pressure of the spleen. In the presence of phentolamine, 1 μM, dopamine inhibited ³H transmitter overflow to the same extent as in the absence of the alpha adrenoceptor blocking agent. Moreover, when (S-R)-sulpiride, 1 μM, was present throughout the experiment, the inhibitory effects obtained with α-methylnorepinephrine were not antagonized. These results indicate that in the perfused cat spleen dopamine and apomorphine inhibit the stimulation evoked release of norepinephrine by acting on presynaptic inhibitory dopamine receptors which differ from the presynaptic alpha adrenoceptors. In addition the (S)-stereoisomer of sulpiride antagonized effectively the apomorphine induced inhibition of [³H]norepinephrine overflow while the same concentration of the (R)-isomer was inactive, indicating that the presynaptic dopamine receptors of the spleen are stereoselective. The perfused cat spleen appears to be a useful model for the study of drugs acting on presynaptic inhibitory dopamine receptors.