Loiacono R E, Mitchelson F J
School of Pharmacology, Victorian College of Pharmacy, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Jul;342(1):31-5. doi: 10.1007/BF00178968.
The effect of nicotine (1-10 microM) and tacrine (9-amino-1,2,3,4-tetrahydroacridine; THA) on stimulation evoked release of [3H]acetylcholine from the rat brain slice preparation preincubated with [3H]choline was investigated. In these preparations, nicotine enhanced while tacrine inhibited evoked [3H]acetylcholine release. These effects were blocked by (+)tubocurarine (1 microM) and atropine (0.1 microM) respectively. In the presence of idazoxan (0.3 microM) plus atropine (0.1 microM), nicotine (3 microM) continued to enhance evoked [3H]acetylcholine release while the inhibitory effect of tacrine (1 microM) on evoked [3H]acetylcholine release was reversed to an enhancement. Under these circumstances the effects of both nicotine and tacrine were blocked by (+)tubocurarine (1 microM). These findings demonstrate that tacrine can both inhibit or enhance [3H]acetylcholine release, most likely through its activity as a cholinesterase inhibitor. Under normal circumstances following tacrine the predominant effect of the elevated levels of acetylcholine will be activation of inhibitory presynaptic muscarine receptors on cholinergic nerves and an inhibition of evoked [3H]acetylcholine release. Under conditions where both presynaptic inhibitory muscarine and alpha 2-adrenoceptors are blocked, the elevated levels of acetylcholine produced by tacrine will lead to the activation of facilitatory presynaptic nicotine cholinoceptors on cholinergic nerves and an enhancement of evoked [3H]acetylcholine release.
研究了尼古丁（1 - 10微摩尔）和他克林（9 - 氨基 - 1,2,3,4 - 四氢吖啶；THA）对用[3H]胆碱预孵育的大鼠脑片标本中刺激诱发的[3H]乙酰胆碱释放的影响。在这些标本中，尼古丁增强而他克林抑制诱发的[3H]乙酰胆碱释放。这些作用分别被（+）筒箭毒碱（1微摩尔）和阿托品（0.1微摩尔）阻断。在咪唑克生（0.3微摩尔）加阿托品（0.1微摩尔）存在的情况下，尼古丁（3微摩尔）继续增强诱发的[3H]乙酰胆碱释放，而他克林（1微摩尔）对诱发的[3H]乙酰胆碱释放的抑制作用则逆转增强。在这些情况下，尼古丁和他克林的作用均被（+）筒箭毒碱（1微摩尔）阻断。这些发现表明，他克林既能抑制也能增强[3H]乙酰胆碱释放，很可能是通过其作为胆碱酯酶抑制剂的活性。在正常情况下，给予他克林后，乙酰胆碱水平升高的主要作用将是激活胆碱能神经上的抑制性突触前毒蕈碱受体并抑制诱发的[3H]乙酰胆碱释放。在突触前抑制性毒蕈碱和α2 - 肾上腺素能受体均被阻断的情况下，他克林产生的乙酰胆碱水平升高将导致胆碱能神经上的易化性突触前尼古丁胆碱受体激活并增强诱发的[3H]乙酰胆碱释放。
