Schistosoma mansoni: neurotransmitters and the mobility of cercariae and schistosomules.
The concentration-dependent action of alkyl-isothiouroniums on Schistosoma mansoni cercariae, ranging from partial to total abolition of locomotor and flame cell movements, and/or suppression of virulence, is due to H1-histamine receptor inhibition. Correspondingly, H1-receptor inhibitors of widely different chemical structure, such as clemizol, diphenhydramine, brompheniramine, and promethazine, in 0.03-0.06 nM concentrations, induced an analogous cercarial immobilization reversed by addition of excess histamine. In contrast, the H2-receptor inhibitors cimetidine and metiamide did not immobilize cercariae. Histamine, acetylcholine, and serotonin, added to cercarial suspensions, showed no direct activity. Their participation in the mechanism of cercarial mobility was shown by the dose-dependent effects of antagonists, such as the serotonin antagonist methysergide and the acetylcholinesterase inhibitor physostigmine. These effects were not reversible by addition of serotonin and acetylcholine, respectively. A histamine-irreversible cercarial immobilization induced by the H-liberator 48/80 suggested that, besides H1-receptor inhibition, H-liberation and/or depletion also participated in mobility and survival. The detection of histamine in the cercaria corroborated the participation of histaminergic mechanisms. S. mansoni schistosomules collected from the mouse lung reacted to H1 antihistamines like cercariae, with a dose-dependent reduction of mobility and somatic deformation, such as vacuolization, granulation, and caecal enlargement.
Ercoli
N
N
Payares
G
G
Nuñez
D
D
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007550:Isothiuronium / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009068:Movement / Q000187:drug effects; D011398:Promethazine / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D014617:Vacuoles / Q000648:ultrastructure
D002800:Cholinesterase Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007550:Isothiuronium; D012701:Serotonin; D006632:Histamine; D004155:Diphenhydramine; D011398:Promethazine; D000109:Acetylcholine; D008784:Methysergide