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L-type Ca2+ channels activation and contraction elicited by myricetin on vascular smooth muscles

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Abstract

The effects of myricetin (3,3’,4’,5,5’,7-hesahydroxyflavone), a natural flavonoid found in edible plants, were studied on vascular smooth muscle L-type Ca2+ channels by comparing its mechanical, radioligand binding, and electrophysiological properties to those of the Ca2+ channel agonist (S)-(-)-Bay K 8644.

In rat aorta rings, both myricetin and (S)-(-)-Bay K 8644 induced contractile responses, which were dependent upon prior exposure to K+. At 15 mM K+ (K15) the pEC50 values for myricetin and (S)-(-)-Bay K 8644 were 4.43±0.03 and 7.92±0.13, respectively. Furthermore, the maximum tension response to myricetin was not significantly different from that elicited by either (S)-(-)-Bay K 8644 or K60. The Ca2+ channel blockers nifedipine, verapamil and diltiazem antagonised and fully reverted myricetin-, (S)-(-)-Bay K 8644- as well as K60-induced contractions. Both myricetin and (S)-(-)-Bay K 8644 potentiated rat aorta ring responses to K+, shifting the K+ concentration-response curve to the left. (S)-(-)-Bay K 8644, but not myricetin, inhibited in a concentration-dependent manner (+)-[3H]PN200–110 binding in porcine aortic membranes. Electrophysiological recordings from single rat tail artery myocytes, under amphotericin B-perforated as well as conventional methods, showed that both myricetin and (S)-(-)-Bay K 8644 increased L-type Ba2+ current (IBa(L)) and shifted the maximum of the current-voltage relationship by 10 mV in the hyperpolarising direction, without, however, modifying the threshold potential. Furthermore, (S)-(-)-Bay K 8644 accelerated both activation and inactivation kinetics of IBa(L) while myricetin slowed down the activation kinetics. Finally, both (S)-(-)-Bay K 8644 and myricetin slowed down deactivation kinetics of IBa(L).

These results suggest that myricetin induces vasoconstriction by activating L-type Ca2+ channel with similar efficacy but a site of action different to that of (S)-(-)-Bay K 8644.

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Abbreviations

IBa(L) :

L-type Ba2+ current

PSS:

Physiological salt solution

Vh :

Holding potential

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Acknowledgements

We wish to thank Dr. Valentina Bravi, Dr. Valentina Quadrini, Dr. Beatrice Camilli and Dr. Alessandra Carretta for the assistance in some experiments and Dr. R. Schulz for a critical reading of the manuscript. (+)-[3H]PN200–110 was a kind gift of Dr. Rosanna Matucci (Dipartimento di Farmacologia, Università degli Studi di Firenze). This work was supported by PAR 60%, Fondazione Monte dei Paschi di Siena, and a grant from Ministero degli Affari Esteri (Rome, Italy) as stipulated by law 212 (26–2-1992).

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  1. Dipartimento di Scienze Anatomiche e Biomediche, Università degli Studi di Siena, via A. Moro 2, 53100, Siena, Italy

    Fabio Fusi, Simona Saponara, Maria Frosini, Beatrice Gorelli & Giampietro Sgaragli

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  1. Fabio Fusi
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  2. Simona Saponara
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  3. Maria Frosini
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  4. Beatrice Gorelli
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  5. Giampietro Sgaragli
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Correspondence to Fabio Fusi.

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Fusi, F., Saponara, S., Frosini, M. et al. L-type Ca2+ channels activation and contraction elicited by myricetin on vascular smooth muscles. Naunyn-Schmiedeberg's Arch Pharmacol 368, 470–478 (2003). https://doi.org/10.1007/s00210-003-0836-y

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