Serotonin release and cell proliferation are under the control of alpha-bungarotoxin-sensitive nicotinic receptors in small-cell lung carcinoma cell lines.
Neuronal type nicotinic acetylcholine receptors (nAchRs) have recently been identified in small-cell lung carcinoma. We here show that both nicotine and cytisine stimulate [3H]serotonin release in a dose-dependent manner; this effect is antagonized by alpha-bungarotoxin (alpha Bgtx) and alpha-conotoxin MI (alpha Ctx). Nicotine and cytisine stimulate in vitro SCLC proliferation and this effect is completely antagonized by both alpha Bgtx and alpha Ctx. By PCR analysis, we demonstrate the presence in SCLC of both the alpha 7 and the beta 2 nAchR subunits mRNA. These data show that nAchRs play an important role in the biology of SCLC, and that alpha Bgtx-sensitive receptors of the alpha 7 subtype are crucially involved in both the secretagogue and mitogenic effects of nicotinic agonists.
Codignola
A
A
CNR Center of Cytopharmacology, University of Milan, Italy.
Tarroni
P
P
Cattaneo
M G
MG
Vicentini
L M
LM
Clementi
F
F
Sher
E
E
D001483:Base Sequence; D002038:Bungarotoxins / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011978:Receptors, Nicotinic / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002038:Bungarotoxins; D017931:DNA Primers; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D012701:Serotonin