Effects of calmodulin and protein kinase C antagonists on muscle in the filariid, Acanthocheilonema viteae.
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.
South Bend Center for Medical Education, Indiana University School of Medicine, Notre Dame 46556, USA.
A J
AJ
Minardi
D
D
Christ
H J
HJ
Saz
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004153:Dipetalonema / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D010704:Phorbols / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D014159:Transducers
D000470:Alkaloids; D002147:Calmodulin; D004791:Enzyme Inhibitors; D010704:Phorbols; D011189:Potassium Chloride; D011493:Protein Kinase C; D019311:Staurosporine; D000109:Acetylcholine; D013110:Sphingosine