Only activated but not non-activated presynaptic α₂-autoreceptors interfere with neighbouring presynaptic receptor mechanisms

Summary

Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic α₂-autoreceptors of effects mediated by presynaptic opioid κ- and adenosine A₁-receptors requires activation of the α₂-receptors. The slices were preincubated with ³H-noradrenaline and then superfused with medium containing desipramine 1 μmol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz.

The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca²⁺-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 μmol/l or yohimbine 0.3 μmol/l. Ethylketocyclazocine (EK; 0.1–10 nmol/l) and R-(−)-N⁶-phenylisopropyladenosine (PIA; 1–1,000 nmol/1) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. — The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 μmol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca²⁺ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine.

The results demonstrate that there is no α₂-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic α₂-adrenoceptor does not interfere with presynaptic opioid κ- and adenosine A₁-receptor mechanisms. It is only when the autoreceptor is activated by released noradrenaline that it attenuates neighbouring presynaptic receptor mechanisms, and this attenuation is removed by α₂-adrenoceptor antagonists.