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Mirabegron, a β 3-adrenoceptor agonist reduced platelet aggregation through cyclic adenosine monophosphate accumulation

Mirabegron, a β 3-adrenoceptor agonist reduced platelet aggregation through cyclic adenosine monophosphate accumulation

Camila Bitencourt Mendes-Silvério, Evandro Marcos Alexandre, Caroline Honaiser Lescano, Edson Antunes, Fabiola Zakia Mónica

Eur J Pharmacol. 2018 Jun 15;829:79-84.

PMID: 29654782

Abstract:

Mirabegron is a β3-adrenoceptor agonist and released on the marked for the treatment of overactive bladder. Because mirabegron is the only β3-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 µM) produced significant inhibitions on platelet aggregation induced by collagen- or thrombin, accompanied by greater intracellular levels of cAMP. The β3-adrenoceptor antagonist L 748,337 (1 µM) and the adenylate cyclase inhibitor, SQ 22,536 (100 µM) reversed the inhibition induced by mirabegron in thrombin-stimulated platelets. The selective antagonists for β1-and β2-adrenoceptors, atenolol and ICI 117,551 (3 µM), 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 β3-adrenoceptor could be beneficial as adjuvant antiplatelet therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP17318319-A	SQ 22,536		17318-31-9	Price

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