Involvement of nitric oxide in inhibitory neuromuscular transmission in equine jejunum.
Abstract: To evaluate the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a transmitter acting through an apamin-sensitive mechanism in mediating inhibitory transmission in the equine jejunal circular muscle, and to determine the distribution of VIP-and NO-producing nerve fibers in the myenteric plexus and circular muscle. Methods: Circular muscle strips were suspended in tissue baths containing an oxygenated modified Krebs solution and attached to isometric force transducers. Responses to electrical field stimulation (EFS), tetrodotoxin, the NO antagonists L-N-nitro-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine, apamin, VIP, authentic NO, and the NO donar sodium nitroprusside were tested. Immunostaining for VIP-like and NADPH diaphorase histochemical staining were performed on paraformaldehyde fixed tissue. Results: Subpopulations of myenteric neurons and nerve fibers in the circular muscle were positive for NADPH diaphorase and VIP-like staining. EFS caused a frequency-dependent inhibition of contratile activity. Tetrodotoxin prevented the EFS-induced inhibition of contractions. L-NAME (200 microM) and apamin (0.3 microM) significantly (P < 0.01) reduced EFS-stimulated inhibition of contractile activity at most frequencies tested. The effects of L-NAME and apamin were additive. In their combined presence, EFS induced excitation instead of inhibition (196.7% increase at 5 Hz, n = 28, P < 0.01). Inhibition of contractile activity by EFS was mimicked by sodium nitroprusside. Authentic NO (3-6 microM) abolished contractile activity. VIP induced a dose-dependent inhibition of contractile activity (89.1 +/- 6.3% reduction at approximately 0.3 microM, n = 16). Antagonism of NO synthesis did not alter the response to VIP. Conclusions: NO, VIP, and a substance acting through an apamin-sensitive mechanism appear to comediate inhibitory transmission in the equine jejunal circular muscle. Conclusions: These findings may suggest new therapeutic targets for motility disorders, such as agents that inhibit the synthesis or actions of NO.
Publication Date: 1996-08-01 PubMed ID: 8836376
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research strives to explain the roles of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a substance interacting through an apamin-sensitive mechanism in mediating the inhibitory transmission in the circular muscle of the equine jejunum. The outcome suggests that NO, VIP, and the apamin-sensitive substance potentially co-mediate the inhibitory transmission in these muscles and may point towards new therapeutic targets for motility disorders.
Research Methods
- The study used strips of circular muscles suspended in tissue baths containing an oxygenated modified Krebs solution and connected to isometric force transducers.
- It tested the responses to electrical field stimulation (EFS), tetrodotoxin, NO antagonists L-N-nitro-arginine-methyl-ester (L-NAME), N-nitro-L-arginine, apamin, VIP, authentic NO, and the NO donor sodium nitroprusside.
- Immunostaining was performed for VIP-like and NADPH diaphorase histochemical staining on paraformaldehyde fixed tissue.
Research Results
- The results identified subpopulations of myenteric neurons and nerve fibers in the circular muscles which were positive for NADPH diaphorase and VIP-like staining.
- EFS caused frequency-dependent inhibition of contractile activity in the muscles.
- The EFS-induced inhibition of contractions was halted by tetrodotoxin.
- The EFS-stimulated inhibition of contractile activity was significantly reduced at most frequencies tested by L-NAME (200 microM) and apamin (0.3 microM).
- It was found that the effects of L-NAME and apamin were additive. In their combined presence, EFS induced excitation instead of inhibition.
- The inhibition of contractile activity by EFS could be mimicked by sodium nitroprusside, while authentic NO abolished contractile activity.
- VIP induced a dose-dependent inhibition of contractile activity; however, antagonism of NO synthesis did not alter the response to VIP.
Conclusions and Therapeutic Implications
- The conclusion of the study notes that NO, VIP, and a substance acting through an apamin-sensitive mechanism appear to comediate inhibitory transmission in the equine jejunal circular muscle.
- These findings provide understanding of how inhibitory mechanisms in muscular activity work, extending previous knowledge regarding muscular physiology in equines.
- A practical application of the findings might be in designing therapeutic strategies for motility disorders, potentially exploiting the roles of NO, VIP, and the apamin-sensitive substance to inhibit the synthesis or actions of NO.
Cite This Article
APA
Rakestraw PC, Snyder JR, Woliner MJ, Sanders KM, Shuttleworth CW.
(1996).
Involvement of nitric oxide in inhibitory neuromuscular transmission in equine jejunum.
Am J Vet Res, 57(8), 1206-1213.
Publication
Researcher Affiliations
- Department of Surgical and Radiological Sciences, University of California, Davis 95616, USA.
MeSH Terms
- Animals
- Apamin / pharmacology
- Electric Stimulation
- Histocytochemistry
- Horses
- In Vitro Techniques
- Isometric Contraction / drug effects
- Jejunum / drug effects
- Jejunum / innervation
- Jejunum / physiology
- Muscle, Smooth / drug effects
- Muscle, Smooth / innervation
- Muscle, Smooth / physiology
- NADPH Dehydrogenase / analysis
- NG-Nitroarginine Methyl Ester / pharmacology
- Neuromuscular Junction / drug effects
- Nitric Oxide / pharmacology
- Nitric Oxide / physiology
- Nitric Oxide Synthase / antagonists & inhibitors
- Nitroarginine / pharmacology
- Nitroprusside / pharmacology
- Synaptic Transmission / drug effects
- Vasoactive Intestinal Peptide / pharmacology
Grant Funding
- DK 41315 / NIDDK NIH HHS
Citations
This article has been cited 4 times.- Dhaese I, Vanneste G, Sips P, Buys ES, Brouckaert P, Lefebvre RA. Small intestinal motility in soluble guanylate cyclase alpha1 knockout mice: (Jejunal phenotyping of sGCalpha1 knockout mice).. Naunyn Schmiedebergs Arch Pharmacol 2009 May;379(5):473-87.
- Koenig J, Cote N. Equine gastrointestinal motility--ileus and pharmacological modification.. Can Vet J 2006 Jun;47(6):551-9.
- Mirza MH, Seahorn TL, Oliver JL, Hosgood G, Moore RM. Detection and comparison of nitric oxide in clinically healthy horses and those with naturally acquired strangulating large colon volvulus.. Can J Vet Res 2005 Apr;69(2):106-15.
- Mirza MH, Oliver JL, Seahorn TL, Hosgood G, Moore RM. Detection and comparison of nitric oxide in clinically normal horses and those with naturally acquired small intestinal strangulation obstruction.. Can J Vet Res 1999 Oct;63(4):230-40.
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