Nitrergic Prejunctional Inhibition of Purinergic Neuromuscular Transmission in the Hamster Proximal Colon

2003 ◽  
Vol 89 (5) ◽  
pp. 2346-2353 ◽  
Author(s):  
Hayato Matsuyama ◽  
AbuBakr El-Mahmoudy ◽  
Yasutake Shimizu ◽  
Tadashi Takewaki
Keyword(s):  
Nitric Oxide ◽  
Nerve Stimulation ◽  
Smooth Muscles ◽  
Circular Muscle ◽  
Single Pulse ◽  
Proximal Colon ◽  
Paired Stimulus ◽  
Physiological Control ◽  
Purinergic Transmission ◽  
Intramural Nerve

Neurogenic ATP and nitric oxide (NO) may play important roles in the physiological control of gastrointestinal motility. However, the interplay between purinergic and nitrergic neurons in mediating the inhibitory neurotransmission remains uncertain. This study investigated whether neurogenic NO modulates the purinergic transmission to circular smooth muscles of the hamster proximal colon. Electrical activity was recorded from circular muscle cells of the hamster proximal colon by using the microelectrode technique. Intramural nerve stimulation with a single pulse evoked a fast purinergic inhibitory junction potential (IJP) followed by a slow nitrergic IJP. The purinergic component of the second IJP evoked by paired stimulus pulses at pulse intervals between 1 and 3 s became smaller than that of the first IJP. This purinergic IJP depression could be observed at pulse intervals <3 s, but not at longer ones, and failed to occur in the presence of NO synthase inhibitor. Exogenous NO (0.3–1 μM), at which no hyperpolarization is produced, inhibited purinergic IJPs, without altering the nitrergic IJP and exogenously applied ATP-induced hyperpolarization. In the presence of both purinoceptor antagonist and nitric oxide synthase (NOS) inhibitor, intramural nerve stimulation with 5 pulses at 20 Hz evoked vasoactive intestinal peptide (VIP)-associated IJPs, suggesting that VIP component may be masked in the IJPs of the hamster proximal colon. Our results suggest that neurogenic NO may modulate the purinergic transmission to circular smooth muscles of the hamster proximal colon via a prejunctional mechanism. In addition, VIP may be involved in the neurotransmitter in the hamster proximal colon.

Nitric oxide suppresses a Ca2+-stimulated Cl− current in smooth muscle cells of opossum esophagus

1998 ◽  
Vol 274 (5) ◽  
pp. G886-G890 ◽  
Author(s):  
Yong Zhang ◽  
Fivos Vogalis ◽  
Raj K. Goyal
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscles ◽  
Reversal Potential ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Patch Clamp Technique ◽  
No Donor ◽  
Pipette Solution

Nitric oxide (NO) hyperpolarizes visceral smooth muscles. Using the patch-clamp technique, we investigated the possibility that NO-mediated hyperpolarization in the circular muscle of opossum esophagus results from the suppression of a Ca2+-stimulated Cl− current. Smooth muscle cells were dissociated from the circular layer and bathed in high-K+Ca2+-EGTA-buffered solution. Macroscopic ramp currents were recorded from cell-attached patches. Contaminating K+-channel currents were blocked with tetrapentylammonium chloride (200 μM) added to all solutions. Raising bath Ca2+concentration above 150 nM in the presence of A-23187 (10 μM) activated a leak current ( I L-Ca) with an EC50 of 1.2 μM at −100 mV. The reversal potential ( E rev) of I L-Ca (−8.5 ± 1.8 mV, n = 8) was significantly different ( P < 0.05) from E rev of the background current (+4.2 ± 1.2 mV, n = 8). Equimolar substitution of 135 mM Cl− in the pipette solution with gluconate significantly shifted E rev of I L-Ca to +16.6 ± 3.4 mV ( n = 4) ( P < 0.05 compared with background), whereas replacement of total Na+with Tris+ suppressed I L-Ca but did not affect E rev(−15 ± 3 mV, n = 3; P > 0.05). I L-Ca was inhibited by DIDS (500 μM). Diethylenetriamine-NO adduct (200 μM), a NO• donor, and 8-bromo-cGMP (200 μM) suppressed I L-Ca by 59 ± 15% ( n = 5) and 62 ± 21% ( n = 4) at −100 mV, respectively. We conclude that in opossum esophageal smooth muscle NO-mediated hyperpolarization may be produced by suppression of a Ca2+-stimulated Cl−-permeable conductance via formation of cGMP.

Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission

1992 ◽  
Vol 262 (3) ◽  
pp. G379-G392 ◽  
Author(s):  
K. M. Sanders ◽  
S. M. Ward
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nerve Stimulation ◽  
Smooth Muscles ◽  
Extracellular Fluid ◽  
Electrical Field Stimulation ◽  
Enteric Neurons ◽  
Field Stimulation ◽  
Gi Tract

Part of the regulation of gastrointestinal (GI) smooth muscles is provided by nonadrenergic noncholinergic (NANC) nerves. Stimulation of these nerves, either by field stimulation or via neural reflex pathways, elicits hyperpolarization of postjunctional smooth muscle membranes referred to as inhibitory junction potentials and relaxation. The transmitter(s) that mediate NANC inhibitory neural transmission have been a controversial topic for nearly 30 years. Recent evidence suggests that nitric oxide (NO) may serve as a NANC inhibitory transmitter in the GI tract. This hypothesis is supported by the following. 1) Immunohistochemical studies have shown that the enzyme necessary for NO synthesis is expressed in enteric neurons. In vitro studies of muscles from nearly all levels of GI tract have also shown that arginine analogues, which inhibit NO synthesis, reduce inhibitory effects of NANC neurotransmission. Effects of arginine analogues can be restored by addition of excess L-arginine, the substrate for NO synthesis. These data suggest that NO can be synthesized by enteric nerves. 2) Bioassays have demonstrated nerve-evoked release of a substance that has been identified as NO during NANC nerve stimulation. Oxyhemoglobin, known to bind to and sequester NO, also blocks NANC responses. These data suggest that NO is released into extracellular fluid during nerve stimulation. 3) Addition of NO causes rapid hyperpolarization of GI smooth muscle cells and relaxes muscles strips. These effects are similar to NANC nerve responses. NO and electrical field stimulation also increase tissue guanosine 3',5'-cyclic monophosphate, which may be the second messenger involved in NANC responses. 4) Removal of NO is easily accomplished by its rapid spontaneous breakdown in physiological solutions. 5) The pharmacology of NO and the NANC neurotransmitter in many preparations is similar, e.g., oxyhemoglobin blocks responses to NANC nerve stimulation and to exogenous NO. In summary, it would appear that many of the criteria necessary for NO to be considered a neurotransmitter have been satisfied.

Noradrenergic, noncholinergic inhibitory junction potentials in rat proximal colon: role of nitric oxide

1995 ◽  
Vol 73 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Rosa Serio ◽  
Flavia Mulé ◽  
Alessandra Postorino
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Proximal Colon ◽  
No Synthase ◽  
Resting Potential ◽  
Rat Colon ◽  
Inhibitory Junction Potential ◽  
Junction Potential

Using a single sucrose gap apparatus, experiments were performed to determine the involvement of nitric oxide (NO) in the generation of noradrenergic, noncholinergic (NANC) inhibitory junction potentials in circular muscle of rat proximal colon. Inhibitors of NO synthase, Nω-nitro-L-arginine and its methyl ester, reduced the amplitude of the electrically evoked inhibitory junction potentials, without affecting membrane resting potential. Such an effect was stereospecific and it was prevented by L-arginine but not by D-arginine. Sodium nitroprusside induced a tetrodotoxin-resistant hyperpolarization, which was not affected by NO synthase inhibitors. Aparnin reduced sodium nitroprusside induced hyperpolarization, as well as NANC inhibitory junction potentials, and α-chymotrypsin decreased the amplitude of electrical field stimulation evoked responses. Residual responses after NO synthase inhibitors or after α-chymotrypsin were further reduced by pretreatment with α-chymotrypsin or NO synthase inhibitors, respectively. These results suggest that, in rat colonic circular muscle, NO plays an important role in NANC inhibitory junction potential generation. However, another mechanism, peptidergic in nature, is also involved.Key words: nonadrenergic noncholinergic nerves, inhibitory junction potential, nitric oxide, rat colon.

Nonadrenergic, noncholinergic inhibition and rebound excitation in canine colon depend on nitric oxide

1992 ◽  
Vol 262 (2) ◽  
pp. G237-G243 ◽  
Author(s):  
S. M. Ward ◽  
H. H. Dalziel ◽  
K. D. Thornbury ◽  
D. P. Westfall ◽  
K. M. Sanders
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Slow Wave ◽  
Nerve Stimulation ◽  
Wave Amplitude ◽  
Inhibitory Response ◽  
Proximal Colon ◽  
Oxide Synthase ◽  
Rebound Excitation

Nonadrenergic, noncholinergic (NANC) nerves regulate slow waves along the submucosal border of the canine proximal colon. Experiments were performed to determine the role of nitric oxide (NO) in NANC responses. NANC responses are characterized by hyperpolarization and reduction in slow-wave amplitude and duration during the period of stimulation. This is followed by a "rebound" excitation (increase in amplitude and duration) of the slow wave immediately after the stimulus. These responses were blocked by L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase and by tetrodotoxin (TTX). Exogenous NO mimicked NANC responses, including the poststimulus rebound excitation. Responses to NO were unaffected by L-NAME or TTX. Responses to NANC nerve stimulation and NO were blocked by oxyhemoglobin but not by methemoglobin. Rebound excitation was reduced by pretreatment with indomethacin, suggesting that an eicosanoid may mediate this phase of NANC responses. Taken together, these data suggest that NO mediates NANC nerve responses in the proximal colon. NO appears to directly cause the inhibitory response, but the rebound response may depend on release of an eicosanoid.

Release of nitric oxide by nerve stimulation in the human urogenital tract

Neuroreport ◽  
1994 ◽  
Vol 5 (6) ◽  
pp. 733 ◽  
Author(s):  
Anna M. Leone ◽  
N. Peter Wiklund ◽  
Tomas Hokfelt ◽  
Lou Brundin ◽  
Salvador Moncada
Keyword(s):  
Nitric Oxide ◽  
Nerve Stimulation ◽  
Urogenital Tract

scholarly journals Quercetin relaxes human gastric smooth muscles directly through ATP‐sensitive potassium channels and not depending on the nitric oxide pathway

2021 ◽  
Author(s):  
Beata Modzelewska ◽  
Krzysztof Drygalski ◽  
Tomasz Kleszczewski ◽  
Andrzej Chomentowski ◽  
Krzysztof Koryciński ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Smooth Muscles ◽  
Nitric Oxide Pathway

Nitric oxide mediates outward potassium currents in opossum esophageal circular smooth muscle

1996 ◽  
Vol 270 (6) ◽  
pp. G932-G938 ◽  
Author(s):  
J. Jury ◽  
K. R. Boev ◽  
E. E. Daniel
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Circular Muscle ◽  
Outward Current ◽  
Equilibrium Potential ◽  
Patch Clamp Technique ◽  
Pipette Solution ◽  
Whole Cell ◽  
Circular Smooth Muscle ◽  
Outward Currents

Single smooth muscle cells from the opossum body circular muscle were isolated and whole cell currents were characterized by the whole cell patch-clamp technique. When the cells were held at -50 mV and depolarized to 70 mV in 20-mV increments, initial small inactivating inward currents were evoked (-30 to 30 mV) followed by larger sustained outward currents. Depolarization from a holding potential of -90 mV evoked an initial fast inactivating outward current sensitive to 4-aminopyridine but not to high levels of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The outward currents reversed near K+ equilibrium potential and were abolished when KCl was replaced by CsCl in the pipette solution. The sustained outward current was inhibited by quinine and cesium. High EGTA in the pipette solution reduced but did not abolish the sustained outward currents, suggesting that both Ca(2+)-dependent and -independent currents were evoked. The nitric oxide (NO)-releasing agents Sin-1 and sodium nitroprusside increased outward K+ currents. High levels of EGTA in the pipette solution abolished the increase in outward current induced by Sin-1. The presence of cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump, blocked the effects of NO-releasing agents. We conclude that NO release activates K+ outward currents in opossum esophagus circular muscle, which may depend on Ca2+ release from the SR stores.

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