Emerging Technologies in the Analysis of C. elegans Nicotinic Acetylcholine Receptors

2016 ◽  
pp. 77-96 ◽  
Author(s):  
Alison Philbrook ◽  
Michael M. Francis
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Emerging Technologies ◽  
Nicotinic Acetylcholine ◽  
C Elegans

Mode of action of levamisole and pyrantel, anthelmintic resistance, E153 and Q57

Parasitology ◽  
2007 ◽  
Vol 134 (8) ◽  
pp. 1093-1104 ◽  
Author(s):  
R. J. MARTIN ◽  
A. P. ROBERTSON
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Receptors ◽  
Anthelmintic Resistance ◽  
Nematode Species ◽  
Single Mutation ◽  
Somatic Muscle ◽  
Nicotinic Acetylcholine ◽  
C Elegans ◽  
Molecular Information

SUMMARYHere we review molecular information related to resistance to the cholinergic anthelmintics in nematodes. The amount of molecular information available varies between the nematode species, with the best understood so far being C. elegans. More information is becoming available for some other parasitic species. The cholinergic anthelmintics act on nematode nicotinic acetylcholine receptors located on somatic muscle cells. Recent findings demonstrate the presence of multiple types of the nicotinic receptors in several nematodes and the numerous genes required to form these multimeric proteins. Not only are the receptors the product of several genes but they are subject to modulation by several other proteins. Mutations altering these modulatory proteins could alter sensitivity to the cholinergic anthelmitics and thus lead to resistance. We also discuss the possibility that resistance to the cholinergic anthelmintics is not necessarily the result of a single mutation but may well be polygenic in nature. Additionally, the mutations resulting in resistance may vary between different species or between resistant isolates of the same species. A list of candidate genes to examine for SNPs is presented.

Lophotoxin-insensitive nematode nicotinic acetylcholine receptors.

1996 ◽  
Vol 199 (10) ◽  
pp. 2161-2168
Author(s):  
C Tornøe ◽  
L Holden-Dye ◽  
C Garland ◽  
S N Abramson ◽  
J T Fleming ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Ascaris Suum ◽  
Xenopus Laevis Oocytes ◽  
Nicotinic Acetylcholine ◽  
Mouse Muscle ◽  
C Elegans ◽  
Naturally Occurring ◽  
Alpha Bungarotoxin

Nematode nicotinic acetylcholine receptors (nAChRs) are molecular targets of several anthelmintic drugs. Studies to date on Caenorhabditis elegans and Ascaris suum have demonstrated atypical pharmacology with respect to nAChR antagonists, including the finding that kappa-bungarotoxin is a more effective antagonist than alpha-bungarotoxin on Ascaris muscle nAChRs. Lophotoxin and its naturally occurring analogue bipinnatin B block all vertebrate and invertebrate nAChRs so far examined. In the present study, the effects on nematode nAChRs of bipinnatin B have been examined. The Ascaris suum muscle cell nAChR was found to be insensitive to 30 mumol l-1 bipinnatin B, a concentration that is highly effective on other nAChRs. To our knowledge, this is the first demonstration of a nAChR that is insensitive to one of the lophotoxins. Xenopus laevis oocytes injected with C. elegans polyadenylated, poly(A+), mRNA also expressed bipinnatin-B-insensitive levamisole responses, which were, however, blocked by the nAChR antagonist mecamylamine (10 mumol l-1). In contrast to the findings for nematode receptors, bipinnatin B (30 mumol l-1) was effective in blocking mouse muscle nAChRs expressed in Xenopus laevis oocytes and native insect nAChRs. A possible explanation for insensitivity of certain nematode nAChRs to lophotoxins is advanced based on the sequence of an alpha-like C. elegans nAChR subunit in which tyrosine-190 (numbering based on the Torpedo californica sequence), a residue known to be critical for lophotoxin binding in vertebrate nAChRs, is replaced by a proline residue.

Nicotinic acetylcholine receptors in the patients with Parkinson's disease: 5IA-SPECT

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S586-S586 ◽  
Author(s):  
Kazuo Hashikawa ◽  
Hidefumi Yoshida ◽  
Nobukatsu Sawamoto ◽  
Shigetoshi Takaya ◽  
Chihiro Namiki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine
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