가토 해마(hippocampus)에서 acetylcholine(ACh) 유리에 미치는 cAMP의 역할에 관한 지견을 얻고자하여 [3H]-choline으로 평형시킨 해마 slice 및 시냅토솜(synaptosome)을 사용하여 [3H]-ACh 유리에 미치는 여러가지 약물들의 영향을 관찰하였다. Adenylate cyclase 활성화제인 forskolin(0.1 ~ 30μM)은 전기 및 고농도 K+ 자극에 의한 [3H]-ACh 유리를 용량 의존적으로 증가시켰으며, dbcAMP 또한 ACh 유리를 강화시켰다. Muscarine성 흥분제인 oxotremorine(0.1 ~ 30μM)은 전기 및 K+ 자극에 의한 [3H]-ACh 유리 효과를 용량 의존적으로 감소시켰으며, 이러한 효과는 forskolin 및 atropine에 의하여 차단됨을 관찰할 수 있었다. 한편 K+-channel 억제제인 glibenclamide(1, 10μM)는 자체로는 K+ 자극에 의한 [3H]-ACh 유리를 약간 억제시킴을 관찰할 수 있었으며, 대량의 forskolin(10μM)에 의한 [3H]-ACh의 증가효과를 감약시킴을 알 수 있었다. 이상의 실험 결과로 가토 해마의 presynaptic muscarinic autoreceptor를 통한 ACh 유리의 조절에는 세포내 cAMP의 관여가 확실하다 하겠으나, 일부 K+-currents의 관여를 배제할 수는 없을 것으로 사료된다.
As it has been reported that the depolarization-induced release of acetylcholine(ACh) is diminished by activation of presynaptic muscarinic autoreceptor in rabbit hippocampus and various lines of evidence indicate the involvement of adenylate cyclase system in ACh release, it was attempted to delineate the role of cAMP in the muscarinic autoreceptor-mediated control of ACh release. Slices and synaptosomal preparations from rabbit hippocampus were incubated with [3H]-choline and the release of the labelled products was evoked either by electrical stimulation or by high-K+, and the influence of various agents on the evoked tritium release was investigated. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from 0.1 to 30μM, increased the [3H]-ACh release in a dose-dependent manner and also dbcAMP increased the tritium outflow. The responses to oxotremorine, a specific muscarinic agonist, were characterized by decrement of ACh release in dose range of 0.1-30μM, and the oxotremorine effects were inhibited either by forskolin or by atropine. Glibenclamide, a specific K+-channel inhibitor, in concentration of 1 ~ 10μM, decreased the evoked ACh release slightly and inhibited the enhancing effect of evoked ACh-release of a large dose(10μM) of forskolin. These results indicate that the cAMP might play a role in the muscarinic ACh receptor-mediated control of ACh rlease in the rabbit hippocampus and suggest that certain potassium currents may also be participated in the post-receptor mechanism of ACh release.
