Endogenous NO inhibits NANC but not cholinergic neurotransmission to circular muscle of guinea pig ileum.
Nitric oxide (NO) mediates neurogenic relaxations of gastrointestinal (GI) smooth muscle. NO synthase (NOS) inhibitors also alter neurogenic contractions, suggesting NO modulates excitatory neurotransmitter release. In circular muscle-myenteric plexus preparations, guanethidine and either scopolamine or CP-96,345, a neurokinin-1 (NK1) receptor antagonist, were used to isolate nonadrenergic, noncholinergic (NANC) or cholinergic contractions, respectively. NOS inhibitors and hemoglobin potentiated neurogenic NANC but not cholinergic contractions and did not affect NK1 receptor agonist [substance P methyl ester (SPME)]-induced contractions. Sodium nitroprusside (SNP), a NO donor, attenuated NANC and cholinergic neurogenic contractions, but cholinergic contractions were less sensitive to SNP. SNP partially attenuated SPME-induced contractions, and apamin reduced inhibition of NANC contractions by SNP. Bethanechol responses were not affected by SNP. These data indicate NANC but not cholinergic contractions are inhibited by endogenous NO, suggesting differential regulation of release of tachykinins and acetylcholine from enteric nerves. NK1 receptor-but not muscarinic receptor-activated postjunctional pathways are also inhibited by NO. Therefore, prejunctional and postjunctional modulation of NANC contractions are mechanisms for inhibition of GI motility by endogenous NO.
Yunker
A M
AM
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
Galligan
J J
JJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation*; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D018723:Bethanechol; D009599:Nitroprusside; D019335:Nitroarginine; D001030:Apamin; D009569:Nitric Oxide; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; C033611:substance P, methyl ester-; D012601:Scopolamine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C066892:CP 96345; D006145:Guanethidine