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Calmodulin inhibitors suppress calcium signaling from serotonin receptors in smooth muscle cells and abolish vasoconstrictive response on intravenous introduction of serotonin

  • Animal and Human Physiology
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Abstract

Comparative study of the effect of calmodulin inhibitors trifluoperazine, W-12, and W-13 and the TRPV1 channel blocker capsazepine on receptor-dependent calcium metabolism in smooth muscle cells of the rat aorta and on the contraction of the isolated rat aorta was performed. Trifluoperazine almost completely abolishes an increase in free cytoplasmic calcium concentration in smooth muscle cells isolated from the rat aorta and smooth muscle cells of the A7r5 line in response to serotonin and does not affect cellular reaction to vasopressin and angiotensin II. W-12 and W-13 also do not attenuate responses to vasopressin and angiotensin II and reduces by two times free cytoplasmic calcium concentration elevation in response to serotonin. The efficiency of calcium metabolism suppression by calmodulin inhibitors correlates with the degree of inhibition of the aorta contractile response to serotonin. It was demonstrated that the inhibitory action of calmodulin antagonists on calcium metabolism in smooth muscle cells and the contractility of the isolated rat aorta during the activation of serotonin vasoconstrictive receptors are realized by a TRPV1-independent mechanism. It was demonstrated in experiments in vivo that trifluoperazine does not influence hypotensive reaction in rats (normally observed in response to intravenous serotonin injection), but removes the hypertensive effect of this neurotransmitter in rats after chronic introduction of dexamethasone. The results obtained confirm the hypothesis (that we previously stated) about the direct involvement of calmodulin in signal transmission from vasoconstrictive serotonin receptors.

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Authors and Affiliations

  1. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, Moscow, 125315, Russia

    L. M. Kozhevnikova, I. L. Zharkikh & P. V. Avdonin

  2. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, ul. Vavilova 26, Moscow, 119334, Russia

    P. V. Avdonin

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  1. L. M. Kozhevnikova
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  2. I. L. Zharkikh
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  3. P. V. Avdonin
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Correspondence to L. M. Kozhevnikova.

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Original Russian Text © L.M. Kozhevnikova, I.L. Zharkikh, P.V. Avdonin, 2013, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2013, No. 4, pp. 437–446.

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Kozhevnikova, L.M., Zharkikh, I.L. & Avdonin, P.V. Calmodulin inhibitors suppress calcium signaling from serotonin receptors in smooth muscle cells and abolish vasoconstrictive response on intravenous introduction of serotonin. Biol Bull Russ Acad Sci 40, 377–385 (2013). https://doi.org/10.1134/S1062359013040080

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