Agonist Concentration-response Models in Mouse and Rabbit Neocortex: Re-evaluation of Classical Models in Comparison with a Recently Developed General Response Function

In the present study concentration-response curves of four a2-adrenoceptor agonists on the a2-autoreceptor-mediated inhibition of [3H]-noradrenaline release in mouse and rabbit neocortex slices were obtained in the absence of autoinhibition. Some of the experiments were performed after short-term presence of phenoxybenzamine to reduce the number and affinity of a2-autoreceptors and after short-term presence of N-ethylmaleimide to destroy the intracellular coupling of a2-autoreceptor-mediated events. Evaluation of the concentration-response curves was done with the double reciprocal method of Furchgott[4], with the operational model of Black et al.[5] and with the general response function of Feuerstein et al.[2]. It was found that both the methods of Furchgott[4] and the operational model of Black et al.[5] were inapplicable to quantify a receptor reserve. Only the general response function appropriately evaluated the receptor reserve in the case of the full agonists used, denied spare receptors for partial agonists and confirmed the absence of spare receptors after pretreatment of the neocortex slices with phenoxybenzamine or N-ethylmaleimide.