Inhibition of acetylcholine-mediated effects by borneol.
We previously reported that the aqueous extract from a medicinal plant Dryobalanops aromatica specifically inhibits the nicotinic acetylcholine receptor (nAChR) (Oh et al. Pharmacol Res 2000;42(6):559-64). Here, the effect of borneol, the main constituent of D. aromatica, on nAChR activity was investigated in bovine adrenal chromaffin cells. Borneol inhibited a nAChR agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)-induced calcium increase with a half maximal inhibitory concentration (IC(50)) of 56+/-9 microM. In contrast, borneol did not affect the calcium increases induced by high K+, veratridine, and bradykinin. The sodium increase induced by DMPP was also inhibited by borneol with similar potency (49+/-12 microM), suggesting that the activity of nAChRs is inhibited by borneol. Borneol inhibited DMPP-induced secretion of [3H]norepinephrine with an IC(50) of 70+/-12 microM. Carbon-fiber amperometry also confirmed the inhibition of DMPP-induced exocytosis by borneol in single chromaffin cells. [3H]nicotine binding, however, was not affected by borneol. The inhibitory effect by borneol is more potent than the effect by lidocaine, a commonly used local anesthetic. The data suggest that borneol specifically inhibits the nAChR-mediated effects in a noncompetitive way.
Park
Tae-Ju
TJ
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, South Korea
Park
Yong-Soo
YS
Lee
Tae-Gyun
TG
Ha
Hyunjung
H
Kim
Kyong-Tai
KT
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D001892:Camphanes / Q000494:pharmacology*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D005089:Exocytosis; D008012:Lidocaine / Q000494:pharmacology; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism
D000779:Anesthetics, Local; D001892:Camphanes; D011978:Receptors, Nicotinic; D009538:Nicotine; D008012:Lidocaine; D012964:Sodium; C022871:isoborneol; D000109:Acetylcholine; D002118:Calcium