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

Abstract

Comparative study of the effect of calmodulin inhibitors (trifluoperazine, W-12, and W-13) and the TRPVI channel blocker (capsazepine) on receptor-dependent calcium exchange in smooth muscle cells of the rat aorta and on the contractility of the isolated aorta was conducted. It was determined that trifluoperazine almost completely removes an increase in the concentration of calcium ions in the cytoplasm of smooth muscle cells (isolated from the rat aorta) and smooth muscle cells of the A7r5 line in response to serotonin and does not influence the cell response to vasopressin and angiotensin II. W-12 and W-13 also do not reduce calcium ion concentration increase (induced by vasopressin and angiotensin II) but reduces by two times its rise in response to serotonin. It was found that the efficiency of calcium exchange suppression by calmodulin inhibitors correlates with the intensity at which they inhibit the contractile response of the aorta on the effect of serotonin. It was detected that the inhibiting effect of calmodulin blockers on calcium exchange in smooth muscle cells and the contractility of the rat isolated 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 introduction), 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.