PRESYNAPTIC ALPHA(2A)-ADRENOCEPTORS REGULATE THE H-3 NORADRENALINE SECRETION IN THE GUINEA-PIG URETHRA

The subtype of the functional presynaptic autoreceptor in adrenergic nerves of the male guinea-pig urethra was pharmacologically characterised. The urethra was incubated with H-3-noradrenaline and superfused with Tyrode solution in vitro and the fractional secretion of H-3-noradrenaline evoked by 300 electrical shocks at 5 Hz was measured. alpha-Adrenoceptor antagonists enhanced the H-3-noradrenaline secretion. The effects of BRL 44408 (+/-)-2-[(4,5-dihydro-1H-imidazol-2yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole), BRL 41992 ((-)-1,2-dimethyl-2,3,9,13b-tetrahydro-1 H-dibenzo[c,f]imidazo[1,5-a]azepine), and WB-4101 (2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane) were tested. The rank order of apparent EC(50) values was BRL 44408<BRL 41992<WB-4101, and correlated best with constants for the alpha(2A)-C10/alpha(2A) adrenoceptor subtype. The results suggest that H-3-noradrenaline secretion in guinea-pig urethra is related by a presynaptic adrenoceptor of the alpha(2A) subtype.