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  • Title: Effects of calmodulin and protein kinase C antagonists on muscle in the filariid, Acanthocheilonema viteae.
    Author: Minardi AJ, Christ D, Saz HJ.
    Journal: J Parasitol; 1995 Dec; 81(6):989-96. PubMed ID: 8544077.
    Abstract:
    Drugs that act on calmodulin and protein kinase C (PKC) were investigated in the filariid Acanthocheilonema viteae. The filariid was slit open longitudinally and attached to an isotonic muscle transducer in a warmed (37 C) chamber containing physiologic solution bubbled with 95% N2-5% CO2. The calmodulin inhibitors, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), increased the spontaneous contractions of the parasite at low concentrations and induced a contraction followed by a flaccid paralysis at high concentrations. Trifluoperazine and W-7 also reduced the contractions from acetylcholine (ACh) and KCl in a concentration-dependent manner. The phorbol esters, phorbol 12-myristate 13-acetate and phorbol 12, 13-dibutyrate, which activate PKC, were either inactive or only weakly active at inducing contractions. Staurosporine (10(-6) M), a PKC inhibitor, enhanced and then blocked the spontaneous contractions of the filariid. Two other PKC inhibitors, H-7 (10(-4) M) and sphingosine (3 x 10(-5) M), induced much smaller increases in the spontaneous contractions and did not inhibit them. Staurosporine and sphingosine inhibited the ACh contractions; however, staurosporine only slightly reduced the maximal KCl contraction. These results support a role for calmodulin, but not for PKC, in filarial muscle contraction.
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