Nicotine facilitates glycine release in the rat spinal dorsal horn.
1. Nicotinic effects on glycine release were investigated in slices of lumbar spinal cord using conventional whole-cell recordings. In most of the substantia gelatinosa (SG) neurons tested, nicotine increased the frequency of the glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs). In a smaller proportion, nicotine evoked not only this same presynaptic response but also a postsynaptic response. 2. Nicotinic facilitation of glycinergic mIPSCs was investigated in mechanically dissociated SG neurons using nystatin-perforated patch recordings. Nicotine (3 x 10(-6) to 10(-5) M) reversibly enhanced the frequency of glycinergic mIPSCs without altering their amplitudes, thus indicating that nicotine facilitates glycine release through a presynaptic mechanism. 3. Choline, a selective alpha7 subunit of nicotinic acetylcholine receptor (nAChR) agonist, had no effect on the mIPSC frequency while anatoxin A, a broad-spectrum agonist of nAChR, facilitated the mIPSC frequency. 4. alpha-Bungarotoxin, a selective alpha7 subunit antagonist, failed to block the nicotinic facilitatory action. Mecamylamine, a broad-spectrum nicotinic antagonist, reversibly inhibited nicotinic action. Dihydro-beta-erythroidine, a selective antagonist of nAChRs containing alpha4-beta2 subunits, completely blocked nicotinic action. 5. Ca(2+)-free but not Cd(2+)-containing bath solutions blocked nicotinic actions. 6. We therefore conclude that nicotine facilitates glycine release in the substantia gelatinosa of the spinal dorsal horn via specific nAChRs containing alpha4-beta2 subunits. This action on a subset of presynaptic nAChRs may underlie nicotine's modulation of noxious signal transmission and provide a cellular mechanism for the analgesic function of nicotine.
Kiyosawa
A
A
Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Katsurabayashi
S
S
Akaike
N
N
Pang
Z P
ZP
Akaike
N
N
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002794:Choline / Q000494:pharmacology; D000087522:Cyanobacteria Toxins; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D008387:Marine Toxins / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D052998:Microcystins; D009411:Nerve Endings / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism; D013376:Substantia Gelatinosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014326:Tropanes; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000779:Anesthetics, Local; D001427:Bacterial Toxins; D002038:Bungarotoxins; D015220:Calcium Channels; C579165:Chrna7 protein, rat; D000087522:Cyanobacteria Toxins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D008387:Marine Toxins; D052998:Microcystins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D014326:Tropanes; D064569:alpha7 Nicotinic Acetylcholine Receptor; D004079:Dihydro-beta-Erythroidine; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D008464:Mecamylamine; D009538:Nicotine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; C509783:anatoxin a; D014633:Valine; D002794:Choline; D002118:Calcium; D005998:Glycine; D001640:Bicuculline