Presynaptic alpha 2A-adrenoceptors regulate the 3H-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 3H-noradrenaline and superfused with Tyrode solution in vitro and the fractional secretion of 3H-noradrenaline evoked by 300 electrical shocks at 5 Hz was measured. alpha-Adrenoceptor antagonists enhanced the 3H-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-1H-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 EC50 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 3H-noradrenaline secretion in guinea-pig urethra is regulated by a presynaptic adrenoceptor of the alpha 2A subtype.