Antagonists of nitric oxide synthesis inhibit nerve-mediated relaxations of longitudinal muscle in guinea pig ileum.
Enteric inhibitory nerves release nonadrenergic, noncholinergic (NANC) transmitters onto the muscle layers of guinea pig ileum. Nitric oxide (NO), released from endothelial cells, relaxes vascular smooth muscle and NO may also be a chemical messenger released from neurons. The present study investigated the possibility that NO is a NANC transmitter in guinea pig ileum longitudinal muscle myenteric plexus. Segments of longitudinal muscle myenteric plexus were maintained in scopolamine-containing (1 microM) Krebs' solution. Histamine (1 microM) was used to induce tone, and NANC relaxations were produced by trains of transmural electrical stimuli. NANC responses consisted of a fast relaxation (approximately 1 s duration) followed either by a slow relaxation or a slow contraction (approximately 4 s duration). The NO-synthase inhibitors, NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester, inhibited peak (fast) neurogenic relaxations by a maximum of 62 +/- 6%, 91 +/- 3% and 50 +/- 3%, respectively. NO-synthase inhibitors either completely blocked the slow relaxation revealing a late contraction or increased the amplitude of late contractions. The actions of NG-monomethyl-L-arginine were partially reversed by L-arginine (1 mM) while the actions of NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine were not consistently reversed by L-arginine. L-Arginine itself did not alter neurogenic responses. NG-monomethyl-D-arginine (10-300 microM) did not affect NANC relaxations or contractions. Hemoglobin (10 microM) inhibited peak NANC relaxations by 45 +/- 4% and increased the amplitude of late contractions without affecting papaverine-induced relaxations. Sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate mimicked NANC relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
L E
LE
Osthaus
J J
JJ
Galligan
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation* / Q000378:metabolism; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D018377:Neurotransmitter Agents / Q000096:biosynthesis* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D019323:omega-N-Methylarginine
D018377:Neurotransmitter Agents; D010108:Oxyhemoglobins; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D010208:Papaverine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester