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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Botto, H. Rouget, C. Maiga, A. Camparo, P. Guérard, M. Lluel, P. Gilles, N. Guilloteau, V. Palea, S. Rekik, M. Rischmann, P. |
| Description | Author Affiliation: Palea S ( UROsphere, Faculté des Sciences Pharmaceutiques, Toulouse, France. stefano.palea@urosphere.com) |
| Abstract | BACKGROUND AND PURPOSE: ρ-Da1a, a 65 amino-acid peptide, has subnanomolar affinity and high selectivity for the human (1) (A) -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 (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-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 (1) (A) -adrenoceptors and on human prostatic strips, ρ-Da1a inhibited adrenaline- and noradrenaline-induced effects. In anaesthetized rats, ρ-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 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 (10 µg·kg(-1) ), whereas tamsulosin significantly reduced PHE effects at doses between 10 and 150 µg·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 (1A) -adenoceptors identified to date and could be a new treatment for various urological diseases. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 168 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2013-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Alpha-1 Receptor Antagonists Pharmacology Elapid Venoms Peptides Prostate Drug Effects Adrenergic Alpha-Agonists Anesthesia Animals Blood Pressure COS Cells Cercopithecus Aethiops Epinephrine Muscle Contraction Muscle, Smooth Physiology Norepinephrine Phenylephrine Prostatic Hyperplasia Metabolism Rats, Wistar Receptors, Adrenergic, Alpha-1 Sulfonamides Urethra Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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