The influence of 2-chloroadenosine on potassium-evoked and neurally-evoked acetylcholine secretion from normal or from latent active zones in the frog.
1. It has been suggested that adenosine receptor agonists do not impair K-dependent acetylcholine (ACh) secretion at motor nerve endings. If true, this result would be discordant with the conventional theories of adenosine action at the neuromuscular junction. It was thus decided to examine the effect of 2-chloroadenosine on quantal ACh release evoked by different K concentrations at frog motor nerve endings. 2. Quantal ACh release evoked by mild increases in the extracellular K concentration (from 2 mM to 6-11 mM) was inhibited by 2-chloroadenosine (10 microM) in a manner similar to the inhibition of neurally-evoked ACh release. 3. ACh secretion evoked by prolonged exposure to 20 mM K Ringer was also inhibited by adenosine derivatives. Under these conditions, alterations in the structure of the secreting active zones have been reported whereby the original release sites now release only a small proportion of the total quantal ACh output. 4. Preparations were bathed for several hours with Ca-free Ringer containing Mg to examine further the importance of intact active zones on inhibition produced by adenosine receptor agonists. This procedure has been reported to produce latent sites of ACh secretion and persistent derangement of the active zones. Shortly after this treatment, neurally-evoked ACh release in normal Ringer solution was found to be inhibited by 2-chloroadenosine (1-5 microM) or adenosine (50 microM). 5. The results suggest that (a) K-evoked ACh release is inhibited by adenosine derivatives even when quantal secretion occurs outside the original active zone and that (b) the cytoskeletal or membrane structures which maintain the structural integrity and lateral regularity of the active zones are not the target sites for inhibition by adenosine derivatives.
Silinsky
E M
EM
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
D015762:2-Chloroadenosine; D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004594:Electrophysiology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology*; D011894:Rana pipiens
D015762:2-Chloroadenosine; D008274:Magnesium; D000241:Adenosine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium