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.
Alberts
P
P
Department of Pharmacology, Pharmacia Pharmaceuticals, Uppsala, Sweden.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003984:Dibenzazepines / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D016014:Linear Models; D008297:Male; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014316:Tritium; D014521:Urethra / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D003984:Dibenzazepines; D004146:Dioxanes; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; C072126:BRL 41992; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D009638:Norepinephrine; C072125:BRL 44408