Noncompetitive inhibition by camphor of nicotinic acetylcholine receptors.
The effect of camphor, a monoterpenoid, on catecholamine secretion was investigated in bovine adrenal chromaffin cells. Camphor inhibited [3H]norepinephrine ([3H]NE) secretion induced by a nicotinic acetylcholine receptor (nAChR) agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), with a half-maximal inhibitory concentration (IC50) of 70 +/- 12 microM. In addition, camphor inhibited the rise in cytosolic calcium ([Ca2+]i) and sodium ([Na+]i) induced by DMPP with IC50 values of 88 +/- 32 and 19 +/- 2 microM, respectively, suggesting that the activity of nAChRs is also inhibited by camphor. On the other hand, binding of [3H]nicotine to nAChRs was not affected by camphor. [Ca2+]i increases induced by high K+, veratridine, and bradykinin were not affected by camphor. The data suggest that camphor specifically inhibits catecholamine secretion by blocking nAChRs without affecting agonist binding.
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, 790-784, Pohang, Korea. ktk@postech.ac.kr
T J
TJ
Park
H K
HK
Seo
B J
BJ
Kang
K T
KT
Kim
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002164:Camphor / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D000891:Anti-Infective Agents, Local; D002395:Catecholamines; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D014316:Tritium; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D002164:Camphor; D012964:Sodium; D002118:Calcium; D009638:Norepinephrine