Role of nitric oxide-related inhibition in intestinal function: relation to vasoactive intestinal polypeptide.
This study examined the role of nitric oxide (NO) in tonic inhibition of motor activity in isolated, perfused canine ileal segments. Brief addition of N omega-nitro-L-arginine methyl ester (L-NAME) to the perfusate caused, after a delay, a concentration-dependent persistent increase in tonic and phasic activity of circular muscle. This increased motor activity was prevented or reversed by addition of L- but not D-arginine to the perfusate. Removal of Ca2+ or addition of 10(-7) M omega-conotoxin (GVIA) to the perfusate markedly reduced this response. The motor activity induced by L-NAME was accompanied by loss of distal inhibition and enhanced excitation to low-frequency field stimulation. L-NAME infusion significantly reduced tonic vasoactive intestinal polypeptide (VIP) output, sodium nitroprusside increased VIP output, but L-arginine infusion did not restore VIP output. Atropine (10(-7) M) and/or hexamethonium (10(-4) M) reduced the motor response to L-NAME by 75%. Atropine reduced and hexamethonium nearly abolished VIP output. We conclude that there is tonic Ca(2+)-dependent NO output from perfused intestinal segments dependent on nerves with N-Ca channels, that NO acts to inhibit muscle directly and by inhibiting release of excitatory mediators, and that this output is the primary inhibitory determinant of contractile activity.
Daniel
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EE
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Haugh
C
C
Woskowska
Z
Z
Cipris
S
S
Jury
J
J
Fox-Threlkeld
J E
JE
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007422:Intestines / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000502:physiology*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D011978:Receptors, Nicotinic; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D020866:omega-Conotoxin GVIA; D001120:Arginine; D000109:Acetylcholine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester