Paola Tarroni

Serotonin release and cell proliferation are under the control of α‐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 α‐bungarotoxin (αBgtx) and α‐conotoxin MI (αCtx). Nicotine and cytisine stimulate in vitro SCLC proliferation and this effect is completely antagonized by both αBgtx and αCtx. By PCR analysis, we demonstrate the presence in SCLC of both the α7 and the β2 nAchR subunits mRNA. These data show that nAchRs play an important role in the biology of SCLC, and that αBgtx‐sensitive receptors of the α7 subtype are crucially involved in both the secretagogue and mitogenic effects of nicotinic agonists.

Neuronal‐type nicotinic receptors in human neuroblastoma and small‐cell lung carcinoma cell lines

A β subunit of the neuronal nicotinic receptor, sharing 88% homology with the rat β4 subunit, has been cloned from a human neuroblastoma cell line. The gene encoding the human β4 subunit is expressed in association with the α3 gene in neuroblastoma and small‐cell lung carcinoma cell lines. Patch‐clamp experiments and radioligand binding assays confirm that these neuroendocrine tumor cell lines express functional neuronal nicotinic receptors. We suggest that these receptors might play a crucial role in the control of neurotransmitter and hormone secretion from neurosecretory human tumors.

Molecular cloning of human neuronal nicotinic receptor α3-subunit

Neuronal nicotinic receptors (nAchRs) have been isolated or cloned in insect, bird and mammalian neurons, but no information exists on the primary structure of human neuronal nAchRs. By screening a cDNA library from the human neuroblastoma cell line IMR 32 with a cDNA probe corresponding to the full length of rat alpha 3-nicotinic subunit, we have identified an open reading frame encoding a protein of 502 amino acids. This protein shows all the features of members of the ligand-gated receptor superfamily and has two cysteine residues at positions 192, 193 which are typical of the nicotinic alpha-subunits. Because of its high homology to rat alpha 3 (93% amino acid identity), we conclude that we have cloned the human alpha 3-nicotinic subunit.

Nicotinic Acetylcholine Receptors in the Human Nervous System

Nicotinic acetylcholine receptors (AChR) are key molecules that mediate chemical communications between cells in various parts of the body: at the neuromuscular junction, in autonomic ganglia and in several areas of the brain. The activation of AChR by the acetylcholine (ACh) released from nerve terminals induces an influx of cations, mainly Na+ ions, through the cell membrane, consequently depolarizing the target cell.

The Neuronal Nicotinic Receptor Family

Acetylcholine (ACh) was one of the earliest neurotransmitters to appear during the course of evolution and acetylcholine receptors (AChRs) are one of the most common receptors in the nervous system (1). Several molecules have evolved as Acetylcholine receptors and they have been classically divided into two large families: muscarinic and nicotinic receptors. Nicotinic receptors (nAChRs) mediate chemical communication between cells in many parts of the body: at the neuromuscular junction, in autonomic ganglia of the peripheral nervous system and in several areas of the brain.