Effects of [rho]-Da1a a peptidic [alpha]1A-adrenoceptor antagonist in human isolated prostatic adenoma and anaesthetized rats

• Published in: British journal of pharmacology 2013-02, Vol.168 (3), p.618
• Main Authors: Palea, S, Maiga, A, Guilloteau, V, Rekik, M, Guerard, M, Rouget, C, Rischmann, P, Botto, H, Camparo, P, Lluel, P, Gilles, N
• Format: Article
• Language: English
• Subjects: Rodents; Tumors
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2012.02231.x

Background and Purpose ρ-Da1a, a 65 amino-acid peptide, has subnanomolar affinity and high selectivity for the human [alpha]1A-adrenoceptor subtype. The purpose of this study was to characterize the pharmacological effects of ρ-Da1a on prostatic function, both in vivo and in vitro. Experimental Approach ρ-Da1a was tested as an antagonist of adrenaline-induced effects on COS cells transfected with the human [alpha]1A-adrenoceptor as well as on human isolated prostatic adenoma obtained from patients suffering from benign prostatic hyperplasia. Moreover, we compared the effects of ρ-Da1a 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 [alpha]1A-adrenoceptors and on human prostatic strips, ρ-Da1a inhibited adrenaline- and noradrenaline-induced effects. In anaesthetized rats, ρ-Da1a and tamsulosin administered i.v. 30min before PHE significantly antagonized the effects of PHE on IUP. The pKB values for tamsulosin and ρ-Da1a for this effect were similar. With regards to AP, ρ-Da1a only reduced the effect of PHE on AP at the lowest dose tested (10µg·kg-1), whereas tamsulosin significantly reduced PHE effects at doses between 10 and 150µg·kg-1. Conclusions and Implications ρ-Da1a 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-Da1a is more uroselective than tamsulosin. ρ-Da1a is the most selective peptidic antagonist for [alpha]1A-adenoceptors identified to date and could be a new treatment for various urological diseases. [PUBLICATION ABSTRACT]