Lack of interaction between alpha(2)-autoreceptors and prejunctional receptors mediating a facilitatory effect on noradrenaline release

The present study was undertaken to investigate the effect of alpha(2)-auto receptor blockade on the facilitatory influence exerted by activation of be ta-, A(2A)-adenosine- and angiotensin II receptors. Segments of a rat-tail artery, previously incubated with H-3-noradrenaline, were subjected to elec trical stimulation. The influence of isoprenaline, the compound CGS21680 an d angiotensin II on the overflow of tritium evoked by electrical stimulatio n was checked before and after alpha(2)-adrenoceptor blockade. All the agon ists used caused concentration-dependent increases of tritium overflow, the maximal effect representing increases of 44.2, 27.4 and 41.2% for isoprena line, CGS21680 and angiotensin II, respectively. In the presence of alpha(2 )-adrenoceptor blockade by phenoxybenzamine (1 mu M) or yohimbine (33 or 10 0 nM), the facilitatory influence of isoprenaline, CGS21680 and angiotensin II was not significantly changed. Since this facilitatory influence, which involves the activation of G(s)- or G(q)-proteins, was not enhanced by alp ha(2)-adrenoceptor blockade, it is concluded that the enhancement of the ne gative modulation resulting from activation of A(1)-adenosine-, muscarine- and kappa-receptors, as previously shown, should be due to the fact that th e involved systems share signal transduction mechanisms, or at least G-prot eins. (C) 2000 Academic Press.