| First Author | Carroll PT | Year | 1985 |
| Journal | Brain Res | Volume | 358 |
| Issue | 1-2 | Pages | 200-9 |
| PubMed ID | 4075114 | Mgi Jnum | J:263491 |
| Mgi Id | MGI:6189683 | Doi | 10.1016/0006-8993(85)90964-3 |
| Citation | Carroll PT (1985) The effect of the acetylcholine transport blocker 2-(4-phenylpiperidino) cyclohexanol (AH5183) on the subcellular storage and release of acetylcholine in mouse brain. Brain Res 358(1-2):200-9 |
| abstractText | The effect of the acetylcholine (ACh) transport blocker 2-(4-phenylpiperidino) cyclohexanol (AH5183) on the subcellular storage and release of acetylcholine was studied in mouse forebrain. Results indicated that AH5183 reduced the amount of ACh released from mouse forebrain minces by high K+ and veratridine over the identical concentration range as it inhibits the active transport of ACh into synaptic vesicles isolated from the electric organ of Torpedo. However, AH5183 did not block the K+- or veratridine-induced reduction of cytoplasmic (S3) ACh. Also, it did not block the loss of vesicular (P3) ACh caused by these depolarizing agents. It did, however, cause a disappearance of nerve ending ACh which was partially matched by a selective gain in the choline content of the P3 fraction. When minces of mouse forebrain were pretreated in high K+ to deplete the S3 and P3 fractions of their ACh content and then subsequently incubated in normal Krebs with [14C]choline, AH5183, at a concentration which reduces ACh release by 50%, did not affect the repletion of P3 stores with newly synthesized [14C]ACh. At somewhat higher concentrations, however, AH5183 reduced the amount of [14C]ACh in the P3 fraction without affecting the amount of [14C]ACh in the S3 fraction. At these concentrations it did not inhibit extracellular choline transport or ChAT activity. These results suggest that AH5183 may reduce the amount of ACh released from central cholinergic nerve terminals in response to depolarization through a combination of effects: (1) it may facilitate the breakdown or loss of ACh stored in the vesicular fraction; (2) it may also block the transport of newly synthesized ACh into the vesicular fraction. |
