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(S)-reticuline induces vasorelaxation through the blockade of L-type Ca2+ channels

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Abstract

In Brazil, various species of the genus Ocotea are used in folk medicine for treating several diseases. The chemical characterization of this plant showed the presence of alkaloids belonging to the benzyltetrahydroisoquinoline family, the major component of which is (S)-reticuline. The present study investigated whether (S)-reticuline exerts an inhibitory effect on smooth muscle L-type Ca2+ channels. Tension measurements and patch clamp techniques were utilized to study the effects of (S)-reticuline. Whole-cell Ca2+ currents were measured using the A7r5 smooth muscle cell line. (S)-reticuline antagonized CaCl2- and KCl-induced contractions and elicited vasorelaxation. It also reduced the voltage-activated peak amplitude of I Ca,L in a concentration-dependent manner. (S)-reticuline did not change the characteristics of current density vs. voltage relationship. (S)-reticuline shifted leftwards the steady-state inactivation curve of I Ca,L. The application of dibutyryl cyclic adenosine monophosphate to the cell decreased the amplitude of Ca2+ currents. In cells pretreated with forskolin, an adenylate cyclase activator, the addition of (S)-reticuline caused further inhibition of the Ca2+ currents suggesting an additive effect. The results obtained show that (S)-reticuline elicits vasorelaxation probably due to the blockade of the L-type voltage-dependent Ca2+ current in rat aorta. The reported effect may contribute to the potential cardioprotective efficacy of (S)-reticuline.

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Acknowledgments

This work was supported by the Brazilian Council for Scientific and Technological Development (CNPq) and Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG). JS Cruz, JM Barbosa-Filho, VS Lemos, and IA Medeiros are CNPq fellows. MA Medeiros hold a CNPq scholarship.

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology (LTF), Universidade Federal da Paraíba, João Pessoa, PB, Brazil

    Marcos Antônio A. Medeiros, Xirley P. Nunes, José M. Barbosa-Filho, Isac A. de Medeiros, Demetrius Antonio M. Araújo & Jader S. Cruz

  2. Department of Biochemistry and Immunology, Laboratório de Biologia Cardiovascular, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Marcos Antônio A. Medeiros, Danilo Roman-Campos & Jader S. Cruz

  3. Departament of Physiology and Biophysics, Laboratório de Fisiologia Cardiovascular, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Virginia S. Lemos & José F. Pinho

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  1. Marcos Antônio A. Medeiros
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  2. Xirley P. Nunes
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  3. José M. Barbosa-Filho
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  4. Virginia S. Lemos
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  5. José F. Pinho
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  7. Isac A. de Medeiros
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  8. Demetrius Antonio M. Araújo
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  9. Jader S. Cruz
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Correspondence to Jader S. Cruz.

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Medeiros, M.A.A., Nunes, X.P., Barbosa-Filho, J.M. et al. (S)-reticuline induces vasorelaxation through the blockade of L-type Ca2+ channels. Naunyn-Schmied Arch Pharmacol 379, 115–125 (2009). https://doi.org/10.1007/s00210-008-0352-1

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  • DOI: https://doi.org/10.1007/s00210-008-0352-1

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