Nerve growth factor treatment enhances nicotine-stimulated dopamine release and increases in cyclic adenosine 3':5'-monophosphate levels in PC12 cell cultures.
In order to examine the relationship between cyclic AMP (cAMP) levels and evoked neurotransmitter release, experiments have been performed with cultures of clonal rat PC12 pheochromocytoma cells. Stimulation of the release of endogenous dopamine by nicotine in these cultures is calcium-dependent and blocked by d-tubocurarine, a specific nicotinic cholinergic antagonist. Similarly, nicotine causes increases in cAMP levels in PC12 cell cultures that are calcium-dependent and blocked by d-tubocurarine. Cultures treated for 6 days or longer with 2 X 10(-9) M nerve growth factor (NGF) release a 3- to 4-fold greater amount of dopamine than do control cultures in response to a maximal concentration of nicotine. Correspondingly, nicotine causes a 3-fold greater increase in cAMP levels in the NGF-treated cultures than in the controls. These results suggest that stimulation of the nicotinic cholinergic receptor in PC12 cells results in some manner in the activation of adenylate cyclase and further support the notion that cAMP is involved in the process of neurotransmitter release.
Baizer
L
L
Weiner
N
N
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D010673:Pheochromocytoma; D051381:Rats; D014403:Tubocurarine / Q000494:pharmacology
D009414:Nerve Growth Factors; D009538:Nicotine; D000242:Cyclic AMP; D004298:Dopamine; D014403:Tubocurarine