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.
Park
T J
TJ
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
Seo
H K
HK
Kang
B J
BJ
Kim
K T
KT
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