Effects of ρ‐ D a1a a peptidic α 1 A ‐adrenoceptor antagonist in human isolated prostatic adenoma and anaesthetized rats

Background and Purpose ρ‐ D a1a, a 65 amino‐acid peptide, has subnanomolar affinity and high selectivity for the human α 1 A ‐adrenoceptor subtype. The purpose of this study was to characterize the pharmacological effects of ρ‐ D a1a on prostatic function, both in vivo and in vitro . Experimental Approach ρ‐ D a1a was tested as an antagonist of adrenaline‐induced effects on COS cells transfected with the human α 1 A ‐adrenoceptor as well as on human isolated prostatic adenoma obtained from patients suffering from benign prostatic hyperplasia. Moreover, we compared the effects of ρ‐ D a1a and tamsulosin on phenylephrine ( PHE )‐induced increases in intra‐urethral ( IUP ) and arterial pressures ( AP ) in anaesthetized rats, following i.v. or p.o. administration. Key Results On COS cells expressing human α 1 A ‐adrenoceptors and on human prostatic strips, ρ‐ D a1a inhibited adrenaline‐ and noradrenaline‐induced effects. In anaesthetized rats, ρ‐ D a1a and tamsulosin administered i.v. 30 min before PHE significantly antagonized the effects of PHE on IUP . The pK B values for tamsulosin and ρ‐ D a1a for this effect were similar. With regards to AP , ρ‐ D a1a only reduced the effect of PHE on AP at the lowest dose tested (10 μg·kg −1 ), whereas tamsulosin significantly reduced PHE effects at doses between 10 and 150 μg·kg −1 . Conclusions and Implications ρ‐ D a1a exhibited a relevant effect on IUP and a small effect on AP . In contrast, tamsulosin antagonized the effects of PHE on both IUP and AP . We conclude that ρ‐ D a1a is more uroselective than tamsulosin. ρ‐ D a1a is the most selective peptidic antagonist for α 1A ‐adenoceptors identified to date and could be a new treatment for various urological diseases.