Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices.
1. The mechanism of stimulation of noradrenaline (NA) release by nicotine (NIC) was investigated in human cerebral cortex slices preloaded with 3H-noradrenaline. 2 NIC (10-1000 micro M) increased 3H-NA release in a concentration-dependent manner. 3. NIC (100 micro M)-evoked 3H-NA release was largely dependent on external Ca2+, and was attenuated by omega-conotoxin GVIA (0.1 micro M) but not by nitrendipine (1 micro M). 4. Tetrodotoxin (1 micro M) and nisoxetine (0.1 micro M) attenuated the NIC (100 micro M)-evoked release of 3H-NA. 5. Mecamylamine (10 micro M), dihydro-beta-erythroidine (10 micro M) and d-tubocurarine (30 micro M), but not alpha-bungarotoxin (alpha-BTX, 0.1 micro M), attenuated the NIC (100 micro M)-evoked release of 3H-NA. 6. NIC (100 micro M)-evoked release of 3H-NA was not affected by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 micro M) and D(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 100 micro M), but attenuated by MK-801 (10 micro M). MK-801 (0.1-1000 micro M) displaced the specific binding of 3H-nisoxetine with K(i) values of 91.2 micro M. NIC (100, 300 and 1000 micro M) did not induce 3H-D-aspartate release in human cerebral cortex slices. 7. NIC (100 micro M)-evoked release of 3H-NA was attenuated by 7-nitroindazole (10 micro M), N(G)-nitro-L-arginine methyl ester HCl (L-NAME, 30 micro M), N(G)-monomethyl-L-arginine acetate (L-NMMA, 300 micro M). [(3)H]-NA release induced by NIC (100 micro M) was attenuated by methylene blue (3 micro M) and 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (ODQ, 10 micro M), and enhanced by zaprinast (30 micro M). 8. In conclusion, NIC stimulates the release of 3H-NA through activation of alpha-BTX-insensitive nicotinic acetylcholine receptors in the human cerebral cortex slices and this action of NIC is associated with modulation of the NO/cGMP pathway.
Woo
Ran-Sook
RS
Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School, Chonju 561-180, Republic of Korea.
Park
Eun-Young
EY
Shin
Min-Soo
MS
Jeong
Min-Suk
MS
Zhao
Rong-Jie
RJ
Shin
Byuong-Soo
BS
Kim
Chul-Jin
CJ
Park
Jin-Woo
JW
Kim
Kee-Won
KW
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D014403:Tubocurarine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D019323:omega-N-Methylarginine
D001120:Arginine; D002118:Calcium; D002121:Calcium Channel Blockers; D004079:Dihydro-beta-Erythroidine; D016291:Dizocilpine Maleate; D004791:Enzyme Inhibitors; D005473:Fluoxetine; D005731:Ganglionic Stimulants; D006162:Guanylate Cyclase; D007191:Indazoles; D008464:Mecamylamine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D018696:Neuroprotective Agents; D009538:Nicotine; D018733:Nicotinic Antagonists; D009568:Nitrendipine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine; D010069:Oxadiazoles; D011688:Purinones; D011810:Quinoxalines; D013779:Tetrodotoxin; D014316:Tritium; D014403:Tubocurarine; D020866:omega-Conotoxin GVIA; C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C092506:N(G)-monomethylarginine acetate; D019323:omega-N-Methylarginine; C011386:nisoxetine; C011145:zaprinast; C080122:7-nitroindazole