Summary
An attempt was made to determinepA2 values of antagonists at the presynaptic, release-inhibiting α2-autoreceptorsof rabbit and rat brain cortex under conditions when there was very little released noradrenaline in the autoreceptor biophase and, hence,pA2 values were not distorted by endogenous autoinhibition. Cortex slices were preincubated with3H-noradrenaline and then superfused and stimulated by trains of 4 pulses delivered at 100 Hz or, in a few cases, by trains of 36 pulses at 3 Hz. The α-adrenoceptor agonists clonidine, noradrenaline, and α-methylnoradren-aline concentration-dependently decreased the stimulation-evoked overflow of tritium. The a-adrenoceptor antagonists yohimbine, rauwolscine and idazoxan did not increase the overflow of tritium elicited by 4 pulses/100 Hz in rabbit brain slices and increased it only slightly in rat brain slices. In contrast, the antagonists increased markedly the overflow at 36 pulses/3 Hz. All antagonists caused parallel shifts to the right of the concentration-response curves of clonidine, noradrenaline, and α-methylnoradrenaline.pA2 values were calculated either from linear regression of log [agonist concentration ratio − 1] on log [antagonist concentration] or from sigmoid curve fitting. The slopes of the linear regression lines were close to unity, and thepA2 values calculated by the two methods agreed well. There was no consistent preferential antagonism of any antagonist to any agonist.pA2 values determined with stimulation by 4 pulses/100 Hz were by 0.53–0.80 log units higher than those determined with stimulation by 36 pulses/3 Hz. ThepA2 values (4 pulses/100 Hz) of yohimbine and rauwolscine in rabbit brain slices (approximately 7.9 and 8.2, respectively), were slightly higher than in rat brain slices (approximately 7.6 and 7.7, respectively), whereas thepA2 value of idazoxan in the rabbit. (about 7.1) was lower than itspA2 value in the rat (about 8.0). The experiments confirm thatpA2 values determined under conditions of autoinhibition are too low. Stimulation with short (30 ms) bursts of pulses permits the estimation ofpA2 values at presynaptic a2-autoreceptors without (rabbit) or almost without (rat) the complication of autoinhibition. The values suggest that α2-adrenoceptors in rabbit brain cortex differ slightly from those in rat brain cortex.
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Limberger, N., Mayer, A., Zier, G. et al. Estimation ofpA2 values at presynaptic α2-autoreceptors in rabbit and rat brain cortex in the absence of autoinhibition. Naunyn-Schmiedeberg's Arch. Pharmacol. 340, 639–647 (1989). https://doi.org/10.1007/BF00717739
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DOI: https://doi.org/10.1007/BF00717739