RT Journal Article SR Electronic T1 Motor Responses in Rat Ileum Evoked by Nitric Oxide Donorsvs. Field Stimulation: Modulation by Pituitary Adenylate Cyclase-Activating Peptide, Forskolin and Guanylate Cyclase Inhibitors JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 23 OP 28 VO 283 IS 1 A1 Ekblad, E. A1 Sundler, F. YR 1997 UL http://jpet.aspetjournals.org/content/283/1/23.abstract AB This study examines nitric oxide (NO) mediated effects on longitudinal muscle with adherent myenteric ganglia from rat ileum in vitro using NO donors and electrical field stimulation. Electrical field stimulation (20 Hz) caused a biphasic response—a relaxation followed by a contraction. NG-nitro-l-arginine methyl ester almost totally abolished the relaxation and l-arginine restored it. The contraction was unaffected. The NO donors sodium-nitroso-N-acetylpenicillamine (SNAP) and sodium-nitroprusside also induced a biphasic response, a contraction followed by relaxation. Relaxations mediated by neuronally released NO were not blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one suggesting that they are independent of a rise in intracellular cyclic guanylate cyclase. Their amplitude was unaffected by forskolin. The relaxations evoked by NO (or a NO-related substance) liberated from SNAP were blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one indicating a cyclic guanylate cyclase-dependent mechanism of action. Pituitary adenylate cyclase-activating peptide and forskolin, but not vasoactive intestinal peptide or neuropeptide Y, caused a marked left-ward shift of the concentration-response curve of the SNAP-induced relaxation. The contractions induced by SNAP were blocked by methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one and thus, cyclic guanylate cyclase dependent. The SNAP-induced contractions were abolished by pituitary adenylate cyclase-activating peptide and forskolin, but unaffected by vasoactive intestinal peptide or NPY. In conclusion, motor responses evoked by NO released from NO donorsvs. neuronally released NO reveals different mechanisms of action. The American Society for Pharmacology and Experimental Therapeutics