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P Kostka, E Jang, EG Watson, JL Stewart and EE Daniel
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
The synaptosomes from canine ileal deep muscular plexus possess a nitric oxide (NO)-sensitive soluble guanylate cyclase, as demonstrated by approximately 3- to 4-fold elevation of synaptosomal cyclic GMP levels in the presence of either 1 mM sodium nitroprusside or L- arginine (20-1,000 microM) plus 1 mM NADPH. The activating effect of L- arginine on synaptosomal soluble guanylate cyclase was related to its enzymatic conversion to citrulline by NO synthase. The synaptosomal NO synthase was found to exhibit both calcium-independent and calcium/calmodulin-dependent components accounting for approximately 2- to 2.5-fold and 7- to 8-fold increases in the basal activity, respectively. The absolute magnitude of these activities was several- fold greater compared to the activities observed in the isolated cells of circular smooth muscle. The synaptosomal Ca-independent and Ca/calmodulin-dependent NO synthase activities were inhibited by methylene blue and L-NG-arginine methyl ester. The NO synthase activity was also attenuated in the presence of cyclic AMP (10 microM). Such an inhibition was related primarily to the suppression of Ca-independent activity. The ability of enteric nerves to generate NO from L-arginine strongly suggests the involvement of this process in the biochemical mechanisms underlying the neurogenic control of intestinal motility.
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