A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves.
The novel alpha-conotoxin Vc1.1 is a potential analgesic for the treatment of painful neuropathic conditions. In the present study, the effects of Vc1.1 were tested on the nicotine-induced increase in excitability of unmyelinated C-fiber axons in isolated segments of peripheral human nerves. Vc1.1 in concentrations above 0.1 microM antagonized the increase in axonal excitability produced by nicotine; the maximal inhibition was observed with 10 microM. We also demonstrate immunoreactivity for alpha 3 and alpha 5 subunits of neuronal nicotinic receptors on unmyelinated peripheral human axons. Blockade of nicotinic receptors on unmyelinated peripheral nerve fibers may be helpful in painful neuropathies affecting unmyelinated sympathetic and/or sensory axons.
Lang
Philip M
PM
Department of Anesthesiology, Ludwig-Maximilians University, 80336 Munich, Germany.
Burgstahler
Ralf
R
Haberberger
Rainer V
RV
Sippel
Wolfgang
W
Grafe
Peter
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020916:Conotoxins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000145:classification / Q000378:metabolism*
D002121:Calcium Channel Blockers; D020916:Conotoxins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine