Pharmacological evaluation of contractile activity of the dog heartworm Dirofilaria immitis

Abstract

Effects of a variety of compounds on spontaneous contractile activity of whole, intact, adult canine heartworms (HW), which had been maintained in culture, were evaluated to improve understanding of the pharmacological sensitivities of this parasitic nematode. Acetylcholine, pilocarpine, imidazole, levamisole, and DL-tetramisole caused spastic paralysis. Gamma-aminobutyrate (GABA), the GABA-mimetic muscimol, the GABA amino transferase inhibitor 3-mercaptopropionic acid, fenthion, ketamine, levodopa, and salinomycin caused flaccid paralysis. Atropine and monensin had inhibitory effects. Neostigmine, the neuromuscular blocking agents decamethonium, succinylcholine, and D-tubocurarine, and the aminergic agents epinephrine, norepinephrine, and serotonin had little or no effect on contractile activity. Thiacetarsamide had a nonreversible, slow onset, inhibitory effect on contractile activity. Occurrence of spastic or flaccid paralysis was not correlated with gender or culture age and was never associated with the same compound. Submaximal stimulatory or inhibitory responses paralleled the type of maximal responses (spastic or flaccid paralysis) for most compounds. Concentration variations producing maximal effects suggested considerable variation in individual preparation sensitivity, which did not appear to involve cuticle defects or time in culture. Difference in gender sensitivity was noted only for levamisole, which caused greater stimulation of contractile activity in males than in females.

Chemotherapeutic Potential of Monensin as an Anti-microbial Agent

“…Pre-treatment with monensin blocked TNFα secretion and activated the innate defence mechanism in mouse macrophage cell line (RAW 264.7) infected with DNA of intestinal protozoan Entamoeba histolytica [78]. In addition, monensin showed an inhibitory effect against a nematode infection, by affecting the contractile activity of Dirofilariaimmitisin dog heartworm [79]. Monensin exhibited activity against Fasciola hepatica-infected rats and adult tegument in culture [80].…”

Ion channels and receptor as targets for the control of parasitic nematodes

“…Exogenous 5-HT also stimulates feeding in A. suum and Nippostrongylus brasiliensis (Brownlee et al, 1997;Trim et al, 2001;Huang et al, 2010). By contrast, it had no effect on the contractile activity of Dirofilaria immitis (Bowen and Vitayavirasak, 2008).…”

Biology of Dirofilaria immitis (Leidy, 1850) (Nematoda: Onchocercidae) and Aedes trivittatus (Coquillett, 1902) (Diptera: Culicidae) in Central Iowa

“…The ability of mosquitoes to function as vectors of filarial worms was first determined by Manson (1878) Conflict of opinion as to the actual vector of D. immitis arose, however, when Breinl (1921) reported the development of D. Immitis within Malpighian tubules of two species of flea, Ctenocephalides felis and canis. Brown and Sheldon (1940) and Summers (1940Summers ( , 1943) also re ported development of 2» immitis in fleas, although Brown and Sheldon discovered developing forms in the Malpighian tubules while Summers found them in the hemocoele. The most extensive study of fleas as vectors of i™m' tis was conducted by Stueben (1954).…”