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The evidence that ATP is released with noradrenaline as a cotransmitter from sympathetic nerve endings in the isolated guinea-pig vas deferens, had led to investigate the potential interactive effects of P2 and alpha 1 receptors, extending the observations to potentially synergistic interactions of histamine-, acetylcholine- and serotonin-receptors. Ineffective concentrations of histamine, carbachol and serotonin increase the neurogenic response to field stimulation; this effect is prevented by the specific antagonist. The responses to the exogenously applied ATP and noradrenaline are increased as well, suggesting that this synergistic interaction of carbachol is less specific. It can be envisaged that receptor complex is a multicomponent system with subunits specific for the primary neurotransmitter and accessory subunits which may interact to increase the responsiveness of the target cell to simultaneous afferent stimuli.

Transdihydrolisuride (terguride), a 9,10-dihydrogenated analogue of the ergot dopamine agonist lisuride, is characterized as partial dopamine receptor agonist at CNS level. This compound was investigated for its effects on peripheral neurotransmission in the attempt to delineate its pharmacological profile. The contractile responses of field-stimulated mouse vas deferens were slightly inhibited by terguride at very high concentrations (10(-5)-10(-2) M); the selective antagonists for alpha 2-adrenergic and dopamine receptors failed to counteract this effect. Terguride was very effective in blocking the inhibitory effects of LY 171555 (selective DA2 agonist), SK&F 38393 (selective DA1 agonist) and clonidine (selective alpha 2 agonist). In no case the antagonism was competitive: the control dose-response curves were not shifted in a parallel and dose-dependent manner. Therefore terguride displays a mixed DA1, DA2 and alpha 2 antagonistic activity.