The effect of nicotine and cytisine on 3H-acetylcholine release from cortical slices of guinea-pig brain.
Nicotine 1.8 X 10(-5)-1.8 X 10(-4) mol/l enhanced the spontaneous 3H-efflux from guinea-pig cortical slices preloaded with 3H-choline and perfused in the presence of hemicholinium (HC-3). The facilitation of tritium outflow was prevented by tetrodotoxin 5 X 10(-7) mol/l and by D-tubocurarine 4.5 X 10(-6) mol/l. Nicotine 1.8 X 10(-6)-1.8 X 10(-4) mol/l, and the agonist cytisine 5 X 10(-7)-5 X 10(-5) mol/l increased, in a concentration-dependent way, 3H-efflux from electrically-stimulated slices (0.2 Hz). The concentration-response curves of both drugs were parallelly shifted to the right by D-tubocurarine 4.5 X 10(-6) mol/l. The EC50 values (i.e. the concentrations required to cause a 50% increase in the S2/S1 ratio) changed for nicotine from 5.58 X 10(-5) to 4.34 X 10(-4) and for cytisine from 6.3 X 10(-6) to 2.75 X 10(-4) mol/l in the absence and in the presence of the antagonist, respectively. In the range of 0.2-2 Hz the magnitude of the effect of nicotine was inversely related to the rate of stimulation. The response to nicotine was subject to rapidly developing tachyphylaxis; it was resistant to atropine. It is concluded that nicotine and cytisine facilitate 3H-efflux from the cholinergic nerve endings of guinea-pig cerebral cortex. This effect involves sodium-dependent mechanisms and is due to an interaction of the drugs with receptors showing affinity for D-tubocurarine.
D000109:Acetylcholine / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001392:Azocines; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D011807:Quinolizines; D013997:Time Factors; D000093843:Quinolizidine Alkaloids
D000109:Acetylcholine; D000470:Alkaloids; D001392:Azocines; D005731:Ganglionic Stimulants; D009538:Nicotine; D011807:Quinolizines; C004712:cytisine; D000093843:Quinolizidine Alkaloids