EFFECTS OF CALMODULIN AND PROTEIN-KINASE-C ANTAGONISTS ON MUSCLE IN THE FILARIID, ACANTHOCHEILONEMA-VITEAE

Drugs act on calmodulin and protein kinase C (PKC) were investigated i n the filariid Acanthocheilonema viteae. The filariid was slit open lo ngitudinally and attached to an isotonic muscle transducer in a warmed (37 C) chamber containing physiologic solution bubbled with 95% N-2-5 % 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 ind uced a contraction followed by a flaccid paralysis at high concentrati ons. Trifluoperazine and W-7 also reduced the contractions from acetyl choline (ACh) and KCI 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 in ducing contractions. Staurosporine (10(-6) M), a PKC inhibitor, enhanc ed 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), i nduced much smaller increases in the spontaneous contractions and did not inhibit them. Staurosporine and sphingosine inhibited the ACh cont ractions; however, staurosporine only slightly reduced the maximal KCI contraction. These results support a role for calmodulin, but not for PKC, in filarial muscle contraction.