RELEASE-INHIBITING ALPHA(2)-ADRENOCEPTORS AT SEROTONERGIC AXONS IN RAT AND RABBIT BRAIN CORTEX - EVIDENCE FOR PHARMACOLOGICAL IDENTITY WITHALPHA(2)-AUTORECEPTORS

The pharmacological properties of the presynaptic alpha(2)-adrenocepto rs modulating the release of serotonin in rat and rabbit brain cortex (alpha(2)-heteroreceptors) were compared with the properties of presyn aptic alpha(2)-autoreceptors in the same brain area. Brain cortex slic es were preincubated with [H-3]-serotonin or [H-3]-noradrenaline and t hen superfused and stimulated by brief high-frequency pulse trains. Th e alpha(2)-adrenoceptor agonist bromoxidine reduced the electrically e voked overflow of tritium in experiments with both [H-3]noradrenaline and [H-3]-serotonin and in brain slices from either species. The antag onists phentolamine, idazoxan, (+)-mianserin, rauwolscine, 5-chloro-4- l-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2-amine (ORG 20350), dimet hoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), (-)-mianserin and corynanthine caused parallel shifts of the concentration-inhibiti on curves of bromoxidine to the right. Negative logarithms of antagoni st dissociation constants pK(d) were calculated from the shifts. In th e rat, the alpha(2)-autoreceptor pK(d) value of each single antagonist was similar to its alpha(2)-heteroreceptor pK(d) value, maximal diffe rence 0.4, giving a close correlation, r = 0.97 (P < 0.001). In the ra bbit equally the alpha(2)-autoreceptor pK(d) value of each single anta gonist was similar to its alpha(2)-heteroreceptor pK(d) value, maximal difference 0.4, again yielding a close correlation, r= 0.96 (P < 0.00 1). However, antagonist pK(d) values at rat alpha(2)-autoreceptors dif fered from those at rabbit alpha(2)-autoreceptors, r = 0.70 (P > 0.05) , and antagonist pK(d) values at rat alpha(2)-heteroreceptors differed from those at rabbit alpha(2)-heteroreceptors, r = 0.64 (P > 0.05). C omparison with radioligand binding experiments from the literature ind icated that, in the rat, both auto- and heteroreceptors conformed best to the alpha(2D) subtype (r equal to or greater than 0.97, P < 0.01 f or pK(d) correlation with binding sites in rat submaxillary gland) whe reas, in the rabbit, they conformed best to the alpha(2A) subtype (r e qual to or greater than 0.93, P < 0.01 for pK(d) correlation with bind ing sites in HT29 cells). It is concluded that, in both the rat and th e rabbit, the alpha(2)-adrenoceptors modulating the release of seroton in are pharmacologically identical with the presynaptic alpha(2)-autor eceptors. However, rat alpha(2)-autoreceptors and -heteroreceptors dif fer pharmacologically from rabbit alpha(2)-autoreceptors and -heterore ceptors. Presynaptic alpha(2)-auto- as well as -heteroreceptors are al pha(2D) in the rat and alpha(2A) in the rabbit.