Presynaptic alpha 2-adrenoceptor, opioid kappa-receptor and adenosine A1-receptor interactions on noradrenaline release in rabbit brain cortex.

The interaction of presynaptic, release-inhibiting alpha 2-adrenoceptors, opioid kappa-receptors and adenosine A1-receptors was studied in slices of the occipito-parietal cortex of the rabbit. The slices were preincubated with 3H-noradrenaline and then superfused and stimulated electrically twice for 2 min each (S1, S2). The stimulation-evoked overflow of tritium was taken to reflect action potential-evoked release of noradrenaline. One of two release-modulating compounds to be examined for interaction was kept in the medium throughout superfusion, the other one was added before S2. In many experiments, the stimulation parameters were adjusted (frequency 0.5-7 Hz; voltage drop 2-5 V/cm) in order to obtain similar reference release (S1) values despite the presence of the first release-modulating compound. The selective kappa-receptor agonist ethylketocyclazocine (EK) attenuated markedly the release-inhibiting effects of the alpha 2-adrenoceptor-selective agonists clonidine and alpha-methylnoradrenaline as well as the release-facilitating effect of the alpha 2-adrenoceptor-selective antagonist yohimbine. The attenuation occurred both when the parameters of electrical stimulation were kept constant and when they were adjusted to obtain similar S1 release values. The selective A1-receptor agonist R-N6-phenylisopropyladenosine (PIA) also attenuated the effects of clonidine and yohimbine. Conversely, clonidine attenuated and yohimbine enhanced the release-inhibiting effect of PIA. Yohimbine also enhanced the release-facilitating effect of the adenosine receptor antagonist 8-phenyltheophylline. Again, these changes occurred both at constant stimulation parameters and when stimulation parameters were adjusted.(ABSTRACT TRUNCATED AT 250 WORDS)