Back to Search
Start Over
Anagyrine desensitization of peripheral nicotinic acetylcholine receptors. A potential biomarker of quinolizidine alkaloid teratogenesis in cattle.
- Source :
-
Research in veterinary science [Res Vet Sci] 2017 Dec; Vol. 115, pp. 195-200. Date of Electronic Publication: 2017 May 02. - Publication Year :
- 2017
-
Abstract
- Anagyrine, a teratogenic quinolizidine alkaloid found in Lupinus spp., is proposed to undergo metabolism by pregnant cattle to a piperidine alkaloid which inhibits fetal movement, the putative mechanism behind crooked calf syndrome. The objective of this study was to test the hypothesis that anagyrine but not lupanine or sparteine can directly, without metabolism, desensitize nicotinic acetylcholine receptors (nAChR) in a cell culture model. SH-SY5Y cells expressing autonomic nAChR, and TE-671 cells expressing fetal muscle-type nAChR were exposed to lupine alkaloids or Dimethylphenylpiperazinium (DMPP) in log <subscript>10</subscript> molar increments from 10nM to 100μM and then to a fixed concentration of acetylcholine (ACh) (10μM for SH-SY5Y cells and 1μM for TE-671 cells) and the responses measured with a membrane potential sensing dye to assess nAChR activation and desensitization. The selective ganglionic nAChR agonist DMPP used as a positive control, was a potent activator and desensitizer of nAChR expressed by SH-SY5Y cells. Lupanine was a weak agonist and desensitizer in SH-SY5Y cells and sparteine was without effect. Anagyrine acted as a partial agonist in both cell lines with EC <subscript>50</subscript> values of 4.2 and 231μM in SH-SY5Y and TE-671 cells, respectively. Anagyrine was a desensitizer of nAChR with DC <subscript>50</subscript> values of 6.9 and 139μM in SH-SY5Y and TE-671 cells, respectively. These results confirm the hypothesis that anagyrine is a potent and effective desensitizer of nAChR, and that anagyrine can directly, without metabolism, desensitize nAChR. Moreover, serum anagyrine concentrations may be a potential biomarker for lupine teratogenicity in cattle.<br /> (Published by Elsevier Ltd.)
- Subjects :
- Animals
Biomarkers
Cattle
Cell Line, Tumor
Female
Humans
Lupinus chemistry
Pregnancy
Quinolizidines blood
Quinolizines pharmacology
Sparteine analogs & derivatives
Sparteine toxicity
Teratogenesis
Teratogens metabolism
Alkaloids pharmacology
Azocines pharmacology
Cattle Diseases blood
Quinolizidines toxicity
Receptors, Nicotinic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1532-2661
- Volume :
- 115
- Database :
- MEDLINE
- Journal :
- Research in veterinary science
- Publication Type :
- Academic Journal
- Accession number :
- 28494312
- Full Text :
- https://doi.org/10.1016/j.rvsc.2017.04.019