Cholinergic signaling at the body wall neuromuscular junction distally inhibits feeding behavior in Caenorhabditis elegans

Abstract

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Pharmacological Profiling of a Brugia malayi Muscarinic Acetylcholine Receptor as a Putative Antiparasitic Target

“…Although it is known that pharyngeal pumping can be modulated by cholinergic signaling in both tissue types, the precise mechanism by which the body wall and pharynx communicate is unclear ( 86 , 94 , 95 ). Interpretations of how pharyngeal pumping is modulated by direct versus indirect pharmacological action at our receptor of interest can be confounded by the promiscuous binding of cholinergic compounds to a range of muscarinic and nicotinic receptors expressed across relevant tissues and perhaps differentially expressed across stages.…”

Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning

“…This inhibition can be restored when nematodes are removed from the drug [36]. Pharyngeal pumping under these conditions directly reflects cholinergic transmission at the body neuromuscular junction that leads to a sustained contraction and shrinkage of the worm [37]. Here, we demonstrate that nematodes exhibit a cholinergic modulation in two different paradigms, the precondition to low doses of the drug and the chronic stimulation with high intoxicating concentrations.…”

Pharmacological profiling of a Brugia malayi muscarinic acetylcholine receptor as a putative antiparasitic target

“…Although it is known that pharyngeal pumping can be modulated by cholinergic signaling in both tissue types, the precise mechanism by which the body wall and pharynx communicate is unclear [83,91,92]. Interpretations of how pharyngeal pumping is modulated by direct versus indirect pharmacological action at our receptor of interest can be confounded by the promiscuous binding of cholinergic compounds to a range of muscarinic and nicotinic receptors expressed across relevant tissues and perhaps differentially expressed across stages.…”

“…In adult stage worms, expression of Bma-gar-3 in the body wall leads to hyperstimulation of pumping in response to CAR, while expression of Bma-gar-3 in both the pharynx and body wall leads to a decreased inhibitory response to ATR compared with either wild-type or gar-3(gk305) strains (Figure 4F). Although it is known that pharyngeal pumping can be modulated by cholinergic signaling in both tissue types, the precise mechanism by which the body wall and pharynx communicate is unclear [83,91,92]. Interpretations of how pharyngeal pumping is modulated by direct versus indirect pharmacological action at our receptor of interest can be confounded by the promiscuous binding of cholinergic compounds to a range of muscarinic and nicotinic receptors expressed across relevant tissues and perhaps differentially expressed across stages.…”