Functional evaluation of inhibition of autonomic transmitter release by autoantibody from Lambert-Eaton myasthenic syndrome.
The effects of the anti-voltage-gated Ca2+ channel (VGCC) antibody obtained from patients with Lambert-Eaton myasthenic syndrome (LEMS) on autonomic neurotransmission were studied in in-vitro experiments. The releases of acetylcholine (ACh) and norepinephrine from the autonomic nerves were evaluated by changes in the contractile responses of guinea pig taenia caeci and left atria to electric field stimulation, respectively. Incubations for 6 hours with LEMS serum and IgG, both of which contain anti-VGCC antibody, markedly suppressed the parasympathetic response but did not affect the sympathetic response. Pharmacological experiments with specific blockers to the VGCC subtypes showed that the Q-type VGCC is closely linked to the genesis of the parasympathetic response. We suggest that the anti-VGCC antibody from the LEMS patients specifically reduces the ACh release from the parasympathetic nerve by binding to the Q-type VGCC.
Houzen
H
H
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Hattori
Y
Y
Kanno
M
M
Kikuchi
S
S
Tashiro
K
K
Motomura
M
M
Nakao
Y
Y
Nakamura
T
T
D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology*; D001681:Biological Assay; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000276:immunology / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D015624:Lambert-Eaton Myasthenic Syndrome / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000737:chemistry*; D010455:Peptides / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D001323:Autoantibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007074:Immunoglobulin G; D010455:Peptides; D011950:Receptors, Cholinergic; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D020866:omega-Conotoxin GVIA