Modulation of acetylcholine release from rat striatal slices: interaction between 4-aminopyridine and atropine.
The objective of these studies was to determine whether the muscarinic receptor-mediated autoregulation of the basal release of acetylcholine (ACh), like the modulation of evoked release, involves 4-aminopyridine (4-AP)-sensitive potassium channels. To accomplish this, striatal and hippocampal slices were incubated with 4-AP in the absence or presence of atropine, and the release of ACh was measured. 4-AP increased the release of ACh in a concentration-dependent manner; a maximal effect (280% of control release) was achieved in the presence of 100 microM. The maximal release of ACh from hippocampal slices was approximately 150% of control release and was achieved in the presence of a broad range of concentrations (33-333 microM 4-AP). Tetrodotoxin (1 microM) totally abolished the 4-AP-induced release of ACh from hippocampal slices, but only attenuated the 4-AP-induced release from striatal slices, i.e., in the presence of tetrodotoxin, the 4-AP-induced release of ACh from the latter was significantly greater than control release by 54%. Atropine (0.1 microM) increased significantly the basal release of ACh from striatal slices by 61%. When striatal slices were incubated with 4-AP in the presence of this maximally effective concentration of atropine, ACh release was significantly greater than release from slices incubated with either atropine or 4-AP alone, suggesting that atropine and 4-AP increase neurotransmitter release by independent mechanisms. Although oxotremorine did not alter either the 4-AP- or atropine-induced release of ACh, it prevented the potentiated response exhibited by slices incubated with both atropine and 4-AP.(ABSTRACT TRUNCATED AT 250 WORDS)
Dolezal
V
V
Department of Pharmacology, Louisiana State University Medical Center, New Orleans.
Wecker
L
L
D015761:4-Aminopyridine / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000378:metabolism*; D004347:Drug Interactions; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D015221:Potassium Channels; D013779:Tetrodotoxin; D010095:Oxotremorine; D001285:Atropine; D015761:4-Aminopyridine; D000109:Acetylcholine