Characterisation of the functional alpha-adrenoceptor subtype in the isolated female pig urethra

The aim of the present study is to characterise the contraction-mediating functional alpha-adrenoceptor of the female pig urethra. Alpha-adrenoceptor reference agonists were used to contract the isolated female pig urethra. The relative intrinsic activity was noradrenaline (1.0), phenylephrine (0.91), methoxamine (0.74), (+/-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane-sulfonanilid e hydrochloride (NS-49) (0.68), oxymetazoline (0.60), dopamine (0.50), clonidine (0.43), midodrine (0.32), ephedrine (0.30), 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304) (0.11), and phenylpropanolamine (0.11). The 21 competitive antagonists used caused parallel rightward shifts in the alpha-adrenoceptor agonist concentration-response curves, giving linear Schild-plots with slopes not significantly different from unity, suggesting that contraction was mediated by a single receptor. The antagonist pK(B) values calculated were R(-)-tamsulosin (9.68), risperidone (9.19), 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-4,4-dimethyl-1,3(2H,4H)-+ ++isoquinolinedione (AR-C 239) (9.09), 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101) (8.87), N-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]-3-methyl-4-oxo-2-phenyl- 4H-1-benzopyran-8-carboxamide monomethanesulfonate (Rec 15/2739/3) (8.81), 5-methylurapidil (8.59), prazosin (8.57), benoxathian (8.56), S(+)-tamsulosin (8.27), indoramin (8.11), doxazosin (7.96), alfuzosine (7.82), phentolamine (7.70), terazosin (7.52), spiperone (7.48), oxymetazoline (7.40), 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]deca ne-7,9-dione dihydrochloride (BMY 7378) (7.05), corynanthine (6.98), rauwolscine (6.40), yohimbine (6.22), and N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dime thyl-1H-indole-3-ethanamine hydrochloride (RS 17053) (6.07). Correlation of subtype-selective antagonist pK(B) values was best with published values for the alpha1a/1A-adrenoceptor subtype. Therefore, the present results suggest that contraction of the female pig urethra is caused by activation of the alpha1A-adrenoceptor.