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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Mirabegron, a beta(3)-adrenoceptor agonist reduced platelet aggregation through cyclic adenosine monophosphate accumulation

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Author(s):
Mendes-Silverio, Camila Bitencourt [1] ; Alexandre, Evandro Marcos [1] ; Lescano, Caroline Honaiser [1] ; Antunes, Edson [1] ; Monica, Fabiola Zakia [1]
Total Authors: 5
Affiliation:
[1] Univ Estadual Campinas, Dept Pharmacol, Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: European Journal of Pharmacology; v. 829, p. 79-84, JUN 15 2018.
Web of Science Citations: 2
Abstract

Mirabegron is a beta(3)-adrenoceptor agonist and released on the marked for the treatment of overactive bladder. Because mirabegron is the only beta(3)-adrenoceptor agonist available and substances that increase the levels of cyclic adenosine monophosphate (cAMP) inhibit platelet activity, we tested the hypothesis that mirabegron could have antiplatelet activity. Collagen- and thrombin induced platelet aggregation, thromboxane B2 (TXB2) and cyclic nucleotides quantification and calcium (Ca2+) mobilization were determined in the absence and presence of mirabegron in human washed platelets. Our results revealed that mirabegron (10 - 300 mu M) produced significant inhibitions on platelet aggregation induced by collagen- or thrombin, accompanied by greater intracellular levels of cAMP. The beta(3)-adrenoceptor antagonist L 748,337 (1 mu M) and the adenylate cyclase inhibitor, SQ 22,536 (100 mu M) reversed the inhibition induced by mirabegron in thrombin-stimulated platelets. The selective antagonists for beta(1)-and beta(2) -adrenoceptors, atenolol and ICI 117,551 (3 mu M), respectively did not interfere on the inhibition induced by mirabegron. In Fluo-4 loaded platelets, mirabegron reduced the total and intracellular Ca2+ levels. Pre-incubation with mirabegron almost abolished the levels of TXB2. Mirabegron did not augment the intracellular levels of cyclic guanosine monophosphate. In conclusion, mirabegron inhibited human platelet aggregation through cAMP accumulation, thus suggesting that substances that activate beta(3)-adrenoceptor could be beneficial as adjuvant antiplatelet therapy. (AU)

FAPESP's process: 13/13907-4 - Evaluation of the effects of opiates agonists in isolated corpus cavernosum from rabbit and rat: does opiate system have role on erectile function?
Grantee:Gilberto de Nucci
Support Opportunities: Regular Research Grants