Involvement of nitric oxide in neuromuscular transmission in canine proximal colon.
The evidence is very strong that NO serves as a neurotransmitter in some autonomic neurons. In the canine proximal colon, NOS is localized in fibers and varicosities of inhibitory motor neurons that course through the muscle layers. Excitation of inhibitory neurons enhances Ca2+ entry into varicosities and activates NOS. In the GI tract enteric inhibitory neurons not only possess the ability to synthesize NO, they may also recycle the by-product, citrulline, back to arginine, thus sustaining inhibitory neurotransmission. NO appears to diffuse freely from nerve terminals and into nearby postjunctional cells. Interstitial cells appear to be innervated by nerves that release NO, and postjunctional effects in these cells include production of cGMP and synthesis of additional NO. In smooth muscle cells NO signals are transduced by guanylate cyclase, the production of cGMP, and activation of protein kinase G, but direct stimulation by NO of some cellular effectors, such as K+ channels also appears to play a role. Responses of smooth muscle cells include activation of K+ channels, inhibition of Ca2+ channels, and a reduction in the sensitivity of the contractile apparatus to Ca2+. All of these factors may contribute to the reduction in mechanical activity produced by stimulation of enteric inhibitory neurons. NO-dependent neurotransmission is critical for many of the physiological processes of the GI tract, such as relaxation of sphincters, gastric accommodation, and receptive relaxation during feeding, and the descending inhibition arc of the peristaltic reflex.
Shuttleworth
C W
CW
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Sanders
K M
KM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D003106:Colon / Q000294:innervation / Q000502:physiology*; D004285:Dogs; D009119:Muscle Contraction; D009469:Neuromuscular Junction / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis; D015221:Potassium Channels / Q000502:physiology; D009435:Synaptic Transmission
D015221:Potassium Channels; D002956:Citrulline; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002118:Calcium