Reversible inhibition of contractions of mammalian cardiomyocytes and of smooth muscle by the protistan parasite Leishmania major

Myotropic neuropeptides have been isolated from vertebrates and invertebrates. Recently, a myoinhibitory peptide from the protist Leishmaniamajor was isolated, and its function in the sand fly vector was described. Similar lysates of cultured L. major were tested for their ability to inhibit contractions in mammalian cell and tissue preparations. L. major proteins (LMP) (34 μg/ml) completely stopped spontaneous contractions of cultured rat cardiomyocytes; cells resumed contracting after a saline wash. An application of 880 μg/ml LMP significantly decreased force of contractions (36%) in strips of guinea pig ileum precontracted with nicotine (p < 0.01) but not with acetylcholine (p > 0.01). Ileal strips rinsed with Tyrode's solution and again stimulated with nicotine contracted normally. Contractile force of ileal strips electrically stimulated with 40 V was reduced in a dose-dependent manner (30, 76, and 100%) (p < 0.01) by increasing concentrations of LMP (220, 440, and 880 μg/ml). This ileal preparation resumed contracting after rinsing with Tyrode's solution. Oxytocin-induced contractions of guinea pig uterine strips were reduced significantly in a dose-dependent manner (21 and 55%) (p < 0.01) by increasing concentrations (170 and 310 μg/ml) of LMP and resumed contracting normally after rinsing with Tyrode's solution. Modes of action for L. major myoinhibitory factors may include either decreasing Ca2+ influx or increasing Ca2+ efflux in susceptible muscle. Protistan-induced inotropism is discussed in light of exacerbating pathology of disease.