Palea_2013_Br.J.Pharmacol_168_618

BACKGROUND AND PURPOSE: rho-Da1a, a 65 amino-acid peptide, has subnanomolar affinity and high selectivity for the human alpha(1) (A) -adrenoceptor subtype. The purpose of this study was to characterize the pharmacological effects of rho-Da1a on prostatic function, both in vivo and in vitro. EXPERIMENTAL APPROACH: rho-Da1a was tested as an antagonist of adrenaline-induced effects on COS cells transfected with the human alpha(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 rho-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(1) (A) -adrenoceptors and on human prostatic strips, rho-Da1a inhibited adrenaline- and noradrenaline-induced effects. In anaesthetized rats, rho-Da1a and tamsulosin administered i.v. 30 min before PHE significantly antagonized the effects of PHE on IUP. The pK(B) values for tamsulosin and rho-Da1a for this effect were similar. With regards to AP, rho-Da1a only reduced the effect of PHE on AP at the lowest dose tested (10 mug.kg(-1) ), whereas tamsulosin significantly reduced PHE effects at doses between 10 and 150 mug.kg(-1) . CONCLUSIONS AND IMPLICATIONS: rho-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 rho-Da1a is more uroselective than tamsulosin. rho-Da1a is the most selective peptidic antagonist for alpha(1A) -adenoceptors identified to date and could be a new treatment for various urological diseases.