Reduction by intracellular calcium chelation of acetylcholine secretion without occluding the effects of adenosine at frog motor nerve endings.
1. The calcium chelators bis-(aminophenoxy)ethane-tetraacetic acid (BAPTA) or dimethyl-BAPTA (DMBAPTA) were introduced into the cytoplasm of frog motor nerve endings by use of the AM loading technique. The effects of intracellular Ca2+ chelation was studied on quantal acetylcholine (ACh) release and on the action of adenosine. 2. Intracellular BAPTA or DMBAPTA prevented the increases in quantal ACh secretion normally evoked by caffeine. 3. Intracellular DMBAPTA decreased the number of ACh quanta released by individual nerve impulses and virtually eliminated the fast phase of facilitation in response to paired nerve impulses. 4. Adenosine reduced both spontaneous and evoked secretion of ACh quanta with its usual potency and efficacy in the presence of intracellular DMBAPTA. Adenosine had no significant effect on facilitation. 5. The results, which suggest that adenosine and intracellular DMBAPTA reduce ACh secretion by different mechanisms, are consistent with the hypothesis that adenosine inhibits ACh release by reducing the ability of Ca2+ to promote ACh secretion from frog motor nerve endings.
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
J M
JM
Hunt
R S
RS
Redman
E M
EM
Silinsky
D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002021:Buffers; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D011894:Rana pipiens
D002021:Buffers; D002614:Chelating Agents; D002110:Caffeine; D004533:Egtazic Acid; C058180:5,5'-dimethyl-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000241:Adenosine; D000109:Acetylcholine; D002118:Calcium