Prejunctional interaction of alpha 2-adrenoceptors and D2 dopamine receptors on perivascular sympathetic nerves.

1. Potential interaction between release-inhibiting prejunctional alpha 2-adrenoceptors and D2 dopamine receptors was investigated by measuring D2 receptor-mediated inhibition of stimulation-evoked tritium overflow from perfused rat tail arteries incubated with [3H]-noradrenaline. 2. In the presence of cocaine (10(-5)M), which enhanced stimulation-evoked tritium overflow, the D2 dopamine agonist N-0923 [(S)-(-) 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin] (10(-8)M) was less effective at inhibiting stimulation-evoked tritium overflow compared to inhibition in the absence of cocaine. 3. In the presence of cocaine, yohimbine (10(-6)M) enhanced stimulation-evoked [3H]-noradrenaline release. Under these conditions, inhibition produced by N-0923 was enhanced compared to tissues without yohimbine. 4. In the presence of cocaine, the alpha 2-adrenoceptor agonist UK-14,304 (10(-7)M) reduced stimulation-evoked tritium overflow. However, in this case, N-0923-mediated inhibition was not significantly altered. 5. In most circumstances increasing or reducing activation of prejunctional alpha 2-adrenoceptors resulted in attenuation or enhancement, respectively, of D2 receptor activation. However, in the case of UK-14,304 this relationship did not hold. Thus, most but not all the evidence supports an interaction between prejunctional alpha 2-adrenoceptors and D2 dopamine receptors.