ACTION OF NICOTINE ON SYMPATHETIC-NERVE TERMINALS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (1) , 133-138
Abstract
Interaction between 4-aminopyridine (4-AP) and nicotine [NT] on sympathetic nerve terminals was studied in the isolated cat spleen slices, labeled with [3H]norepinephrine ([3H]NE). Incubation of slices for 5 min at 37.degree. C in low (50 .mu.M) and high (2 mM) concentrations of NT released 0.8 .+-. 0.08 and 2.73 .+-. 0.39% of tissue [3H]NE. Tetrodotoxin (TTX) blocked the response to low NT but not to high NT. Low NT did not release [3H]NE in the absence of Ca. Response to high NT which persisted in Ca-free solution was blocked by ethylene glycol bis(.beta.-aminoethyl ether)N,N''-tetraacetic acid [EGTA]. 4-AP (1 mM) not only enhanced the response to low NT but it effectively antagonized the suppressant effects of TTX and Ca-free solution on release induced by low NT. Restoration of release by 4-AP from TTX-blocked preparations occurred in the absence of Ca in the perfusion medium, but lanthanum (1 mM) blocked it. Restoration of release from spleen slices incubated in Ca-free Krebs'' solution by 4-AP was blocked by La and prolonged incubation in Ca-free [EGTA] solution. Apparently at lower doses NT, by acting on NT receptors, depolarizes the sympathetic nerve terminals to set off propagated action potentials which are responsible for NE release, and 4-AP restores NT response in the presence of TTX or in the absence of Ca by mobilizing Ca both from extracellular and intracellular sources.