THE PRESYNAPTIC ALPHA-2 AUTORECEPTORS IN PIG BRAIN CORTEX ARE ALPHA-2A

The presynaptic alpha-2 autoreceptors in pig brain cortex were subclas sified in terms of alpha-2A, alpha-2B, alpha-2C and alpha-2D to test t he hypothesis that alpha-2 autoreceptors belong predominantly to the a lpha-2A/D pair of orthologous alpha-2 adrenoceptors. Slices of brain c ortex were preincubated with [H-3]norepinephrine and then superfused a nd stimulated electrically. pK(d) values of 13 alpha-2 adrenoceptor an tagonists (including the partial agonist oxymetazoline) against the al pha-2 agonist 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK 14,304 ) were determined. The stimulation periods used (six pulses at 100 Hz) did not lead to alpha-2 autoinhibilion, as shown by the failure of al l but one of the alpha-2 antagonists to increase the stimulation-evoke d overflow of tritium. UK 14,304 caused a concentration-dependent decr ease of the evoked overflow of tritium, with an EC(50) value of 0.90 n M and a maximal inhibition of 95.2%. All antagonists shifted the conce ntration-inhibition curve of UK 14,304 to the right in a parallel mann er. Antagonist pK(d) values were calculated from the shifts. The pK(d) values at the presynaptic alpha-2 autoreceptors in pig brain cortex c orrelated excellently with pK(d) values at previously subclassified al pha-2A sites but did not correlate significantly or correlated much le ss well with pK(d) values at alpha-2B, alpha-2C and alpha-2D sites. Al so, ratios of K-d values of the antagonists at the presynaptic alpha-2 autoreceptors in pig brain cortex agreed well with ratios at previous ly subclassified alpha-2A sites but not with those at previously subcl assified alpha-2B-D sites. It is concluded that the alpha-2 autorecept ors in pig brain cortex are alpha-2A, in accordance with the hypothesi s mentioned.