Neurotransmitter receptors as central regulators of pancreatic cancer

• Published in: Future oncology (London, England) Vol. 6; no. 2; pp. 221 - 228
• Main Authors: Schuller, Hildegard M, Al-Wadei, Hussein AN
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.02.2010
• Subjects: adrenergic receptor; Animals; Carcinoma, Pancreatic Ductal - physiopathology; Cellular signal transduction; Development and progression; GABA receptor; Humans; Models, Neurological; Neurotransmitter Agents - metabolism; Neurotransmitter receptors; nicotinic acetylcholine receptor; Pancreatic cancer; Pancreatic Neoplasms - physiopathology; Physiological aspects; Receptors, Neurotransmitter - metabolism; Signal Transduction - physiology; stress neurotransmitters; Stress, Physiological - physiology; United States; Yemen
• ISSN: 1479-6694; 1744-8301
• DOI: 10.2217/fon.09.171

Pancreatic ductal adenocarcinoma (PDAC) has a near 100% mortality because it is generally detected at an advanced stage and responds poorly to existing therapeutics. This review summarizes current evidence suggesting important roles of neurotransmitter receptors in the regulation of this malignancy. Experimental evidence indicates that the α -nicotinic acetylcholine receptor (α nAChR) stimulates PDAC via stress neurotransmitter-mediated activation of -adrenergic signaling while the α nAChR inhibits PDAC via GABA-mediated inhibition of adenylyl cyclase activation. In analogy to molecular mechanisms that govern nicotine addiction, chronic exposure to nicotine or its nitrosated derivative nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone render the stimulatory α nAChR hyperactive while desensitizing the inhibitory α nAChR. Accordingly, PDAC intervention strategies should include the diagnosis of unphysiological neurotransmitter levels and aim to restore any imbalance in stimulatory and inhibitory neurotransmitters.