Muscarinic regulation of SCA-9 cells proliferation via nitric oxide synthases, arginases and cyclooxygenases. Role of the nuclear translocation factor kB.

ALEJANDRO J ESPAÑOL; DASSO, MAXIMILIANO; CELLA, MAXIMILIANO; GOREN NORA; MARÍA E. SALES

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Año: 2012 p. 43 - 53

0014-2999

The submandibular gland-derived tumor cell line SCA-9 is considered a useful to study the proliferation signalling pathways and its regulation, which could be activated by different stimuli. It is proposed that the non neuronal cholinergic system, composed by: acethylcholine, the enzime that synthetize and decrate it, and the nicotinic and muscarinic receptors, play a key role in tumorigenesis. here, we investigate the role of muscarinic receptor in SCA-9 cells proliferation, and the modulation of muscarinic signalling pathways exerted by the nucler transcription factor kB (NF-kB).We observed a constitutive expression of all subtypes of muscarinic receptors in SCA-9 cells. The activation of these receptors by carbachol (10-9M) increased cell proliferation. PLC/NOS/arginase pathway is involved in this effect, since carbachol stimulated nitric oxide production, NOS2 and NOS3 expression, urea production and arginase II expression. Also, PLA2/COX pathway is up-regulated in carbachol-induced SCA-9 cells proliferation, because PGE2 liberation is increased and COX-1 expression is turned up. We detected interactions between PLC/NOS/arginase and PLA2/COX pathways via its metabolites. SCA-9 cells exhibit a constitutive activation of NF-kB, and this factor regulates carbachol-induce NOS2 and 3, arginase II and COX-1 expression. In addition, PKC is involved in the up-regulation of NOS2 and arginase II enzymes induced by carbachol via NF-kB. In conclusion, muscarinic receptor activation in SCA-9 tumor cells promotes proliferation via muscarinic receptor effector enzymes, which reveals the participation of NF-kB at this step of tumorigenesis