NICOTINIC RECEPTOR MEDIATES NITRIC-OXIDE SYNTHASE EXPRESSION IN THE RAT GASTRIC MYENTERIC PLEXUS

The mechanism that regulates the synthesis of nitric oxide synthase (N OS), a key enzyme responsible for NO production in the myenteric plexu s, remains unknown, We investigated the roles of the vagal nerve and n icotinic synapses in the mediation of NOS synthesis in the gastric mye nteric plexus in rats, Truncal vagotomy and administration of hexameth onium significantly reduced nonadrenergic, noncholinergic relaxation, the catalytic activity of NOS, the number of NOS-immunoreactive cells, and the density of NOS-immunoreactive bands and NOS mRNA bands obtain ed from gastric tissue, These results suggest that NOS expression in t he gastric myenteric plexus is controlled by the vagal nerve and nicot inic synapses, We also investigated if stimulation of the nicotinic re ceptor increases neuronal NOS (nNOS) expression in cultured gastric my enteric ganglia, Incubation of cultured gastric myenteric ganglia with the nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperizinium (DM PP, 10(-10)-10(-7) M), for 24 h significantly increased the number of nNOS-immunoreactive cells and the density of immunoreactive nNOS bands and nNOS mRNA bands, nNOS mRNA expression stimulated by DMPP was anta gonized by a protein kinase C antagonist, a phospholipase C inhibitor, and an intracellular Ca2+ chelator, We concluded that activation of t he nicotinic receptor stimulates a Ca2+-dependent protein kinase C pat hway, which in turn, upregulates nNOS mRNA expression and nNOS synthes is in the gastric myenteric plexus.