Direct regulation of vascular smooth muscle contraction by mastoparan-7

Abstract

Mastoparan-7 (mas-7) is a basic tetradecapeptide isolated from wasp venom, which activates guanine nucleotide-binding regulatory proteins (G-proteins) and stimulates apoptosis. In smooth muscle cells, mas-7 leads to an increase in the perfusion pressure. The main aim of this study was to evaluate the physiological effect of the direct stimulation of G-proteins in comparison to the typical stimulation of receptors in vascular smooth muscle cells (VSMCs). Experiments were performed on the isolated and perfused tail artery of Wistar rats. The contraction force in our model was measured by an increased level of perfusion pressure with a constant flow. The concentration response curves (CRCs) obtained for mas-7 were sigmoidal. In comparison to the curves for phenylephrine and vasopressin, the mas-7 curve was significantly shifted to the right with a significant reduction in maximal response. Mas-7 significantly increased the perfusion pressure for the intra- and extracellular calcium (Ca2+) influx to the cytoplasm. The presence of the pertussis toxin (PT) did not affect the mas-7-induced contraction. In comparison to phenylephrine and vasopressin, all the values of perfusion pressure following stimulation of the G-proteins by mas-7 were significantly lower. The results of our experiments suggested that mas-7 significantly induces the contraction of VSMCs. The binding site for mas-7 is different from that for PT; thus, PT does not affect VSMC contraction. The tissue effect of this stimulation is comparable to the stimulatory effect of partial agonists. Current knowledge regarding the apoptosis pathway reveals the significance of Ca2+ ions involved in this process. Therefore, mas-7 may induce apoptosis through an increase in the cytoplasmic Ca2+ concentration; however, the use of this mechanism in anticancer therapy must be preceded by a molecule modification that eliminates the vasoconstrictive effect.