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.

Tachykinins mediate noncholinergic excitatory neural responses in the circular muscle of rat proximal colon

1998 ◽  
Vol 76 (6) ◽  
pp. 684-689 ◽  
Author(s):  
R Serio ◽  
F Mulè ◽  
F Bonvissuto ◽  
A Postorino
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Circular Muscle ◽  
Proximal Colon ◽  
Rat Colon ◽  
Neurokinin A ◽  
Receptor Antagonists ◽  
Excitatory Junction Potential ◽  
Excitatory Responses ◽  
Junction Potential

Using the sucrose-gap technique, we attempted to assess a role for tachykinins (TKs) in mediating noncholinergic excitatory junction potential (EJP) and contraction, in the circular muscle of rat proximal colon. Excitatory responses were evoked by submaximal electrical field stimulation (EFS) in the presence of atropine (1 µM), guanethidine (1 µM), indomethacin (10 µM), and Nomega -nitro-L-arginine methyl ester (L-NAME) (100 µM). The NK1 receptor antagonist, SR 140,333 (up to 3 µM) or the NK2 receptor antagonists, SR 48,968 and MEN 10,627 (up to 5 µM) produced a partial inhibition of the excitatory responses to EFS. The co-administration of the selective NK1 and NK2 receptor antagonists produced additive effects on the responses to EFS. Selective NK1 receptor agonist, [Sar9, Met (O2)11]-substance P, induced depolarization and contraction, antagonized by SR 140,333, but not by NK2 receptor antagonists. NK2 receptor agonist, [ betaAla8]-neurokinin A (4-10), also produced electrical and mechanical excitatory effects that were antagonized by SR 48,968 or MEN 10,627, but not by the NK1 receptor antagonist. Our results provide evidence that, in circular muscle of rat colon, endogenous tachykinins are the main excitatory transmitters for nonadrenergic, noncholinergic (NANC) excitation and their action is mediated by both NK1 and NK2 receptors.Key words: NK1 receptor, NK2 receptor, nonadrenergic, noncholinergic (NANC) excitatory junction potential, intestine.

Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle

1991 ◽  
Vol 261 (3) ◽  
pp. G401-G406 ◽  
Author(s):  
J. Murray ◽  
C. Du ◽  
A. Ledlow ◽  
J. N. Bates ◽  
J. L. Conklin
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Inhibitory Effect ◽  
No Synthase ◽  
Maximal Response ◽  
Induced Responses ◽  
Electrical Field ◽  
Esophageal Sphincter ◽  
Esophageal Muscle

Nonadrenergic noncholinergic (NANC) nerves of the opossum esophagus mediate relaxation of circular muscle from the lower esophageal sphincter (LES) and the off contraction of circular esophageal muscle. The latencies between the end of the stimulus and the off contraction describe a gradient so that the latency is longest in muscle from the caudad esophagus. NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthase, and NO were used to test the hypothesis whether NO is a mediator of these nerve-induced responses. Both electrical field stimulation (EFS) of intrinsic esophageal nerves and exogenous NO relaxed LES muscle. Only EFS-induced relaxation was inhibited by L-NNA [half-maximal response (EC50) = 60.0 +/- 20.0 microM]. L-Arginine, the substrate for NO synthase, reversed the inhibitory effect of L-NNA. Exogenous NO did not contact circular esophageal muscle. Both the amplitude (EC50 = 14.7 +/- 4.0 microM) and the latency of the off contraction (EC50 = 41.1 +/- 5.6 microM) were diminished by L-NNA. L-Arginine prevented the action of L-NNA. NG-nitro-L-arginine also attenuated the gradient in the latency of the off response by shortening latencies in muscle from the caudad esophagus. It had no effect on cholinergic nerve-induced contraction of longitudinal esophageal muscle. These data support the hypothesis that NO or an NO-containing compound may be a mediator of NANC nerve-induced responses of the esophagus and LES.

scholarly journals Nitric oxide mediates inhibitory junction potential-independent relaxation of rat proximal colon.

1994 ◽  
Vol 64 ◽  
pp. 213
Author(s):  
Naowarat Suthamnatpong ◽  
Muneaki Hosokawa ◽  
Tadayoshi Takeuchi ◽  
Fumiaki Hata ◽  
Tadashi Takewaki
Keyword(s):  
Nitric Oxide ◽  
Proximal Colon ◽  
Inhibitory Junction Potential ◽  
Junction Potential

Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired cavernosal relaxation with ischemia

2002 ◽  
Vol 282 (6) ◽  
pp. R1730-R1738 ◽  
Author(s):  
Hitoshi Masuda ◽  
Toshihiko Tsujii ◽  
Tetsuo Okuno ◽  
Kazunori Kihara ◽  
Moritaka Goto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Corpus Cavernosum ◽  
Electrical Field Stimulation ◽  
No Synthase ◽  
Field Stimulation ◽  
Electrical Field ◽  
Vessel Occlusion ◽  
Endogenous Inhibitors ◽  
Nos Inhibitors

We examined whether endogenous inhibitors of nitric oxide (NO) synthesis are involved in the impaired cavernosal relaxation with ischemia in rabbits. Two weeks after cavernosal ischemia caused by partial vessel occlusion, endothelium-dependent and electrical field stimulation (EFS)-induced neurogenic NO-mediated relaxations, but not sodium nitroprusside (SNP)-induced relaxation, were significantly impaired in the isolated corpus cavernosum. The Ca2+-dependent NO synthase (NOS) activity and the basal and stimulated cGMP productions with carbachol or EFS were significantly decreased after ischemia. Supplementation of excessl-arginine partially recovered both of the impaired relaxations. The contents of N G-monomethyl-l-arginine (l-NMMA) and asymmetric N G, N G-dimethyl-l-arginine (ADMA) but not l-arginine and symmetric N G, N′G-dimethyl-l-arginine (SDMA) were increased in the cavernosal tissues after ischemia. Authentic l-NMMA and ADMA but not SDMA concentration dependently inhibited both relaxations without affecting the relaxation produced by SNP in the control. Excess l-arginine abolished the inhibition with l-NMMA and ADMA. These results suggest that the impaired NO-mediated cavernosal relaxations after ischemia are closely related to the decreased NOS activity and the increased accumulation of l-NMMA and ADMA.

Modulation of cholinergic neuromuscular transmission by nitric oxide in canine colonic circular smooth muscle

1998 ◽  
Vol 275 (6) ◽  
pp. G1324-G1332 ◽  
Author(s):  
M. G. Rae ◽  
M. A. Khoyi ◽  
K. D. Keef
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Layer ◽  
Cholinergic Transmission ◽  
Circular Smooth Muscle ◽  
Inhibitory Junction Potential ◽  
Excitatory Junction Potentials ◽  
Synthase Inhibitor

This study examines the effect of nitric oxide (NO) on cholinergic transmission in strips of canine colonic circular muscle in which neural plexus-pacemaker regions had been removed. Electrical field stimulation gave rise to atropine- and TTX-sensitive excitatory junction potentials (EJPs), the amplitude of which were frequency dependent. In 47% of control muscles, the EJP was followed by an inhibitory junction potential (IJP), whereas in the presence of atropine all preparations exhibited only IJPs. The NO synthase inhibitor N ω-nitro-l-arginine (l-NNA), the guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxaline-1-one (ODQ), and the protein kinase G (PKG) antagonist Rp-8-bromo-PET-cGMPS all significantly increased EJP amplitude and reduced or abolished IJPs. The potentiation of EJPs by l-NNA was reversed by the NO donors sodium nitroprusside (SNP) and S-nitroso- N-acetylpenicillamine in a manner blocked by ODQ. [14C]ACh overflow was also measured to evaluate the possible prejunctional effects of NO. Both norepinephrine and TTX significantly decreased [14C]ACh overflow; however, l-NNA, ODQ, and SNP were without effect. These data suggest that both cholinergic and nitrergic motoneurons functionally innervate the interior of the circular muscle layer. The inhibitory actions of NO on cholinergic transmission appear to be post- rather than prejunctional and to involve guanylyl cyclase as well as possibly PKG.

Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon

1991 ◽  
Vol 261 (3) ◽  
pp. G553-G557 ◽  
Author(s):  
K. D. Thornbury ◽  
S. M. Ward ◽  
H. H. Dalziel ◽  
A. Carl ◽  
D. P. Westfall ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Proximal Colon ◽  
Biologically Active ◽  
Nerve Terminals ◽  
Open Probability ◽  
Inhibitory Neurotransmission ◽  
Inhibitory Junction Potential ◽  
Transmitter Substance ◽  
Visceral Muscles ◽  
Junction Potential

Previous evidence suggests that nonadrenergic, noncholinergic (NANC) inhibitory neurotransmission in visceral muscles may be mediated by nitric oxide (NO). We have demonstrated that NO and the NO carrier S-nitrosocysteine can mimic the hyperpolarization in colonic muscle caused by nerve stimulation. The finding that S-nitrosocysteine breaks down fast enough to cause inhibitory junction potential (IJP)-like hyperpolarizations suggests that NO could be stored as a nitrosothiol in secretory vesicles in nerve terminals. Oxyhemoglobin blocked hyperpolarization responses to NO and S-nitrosocysteine and NANC IJPs. These findings suggest that NO is a biologically active transmitter substance in NANC inhibitory neurotransmission. NO enhanced the open probability of Ca(2+)-activated K+ channels in isolated colonic muscle cells. These channels may mediate the hyperpolarization response to NANC neurotransmission in colonic muscles.

A mediator derived from arginine mediates inhibitory junction potentials and relaxations in lower esophageal sphincter: an independent role for vasoactive intestinal peptide

1992 ◽  
Vol 70 (8) ◽  
pp. 1182-1189 ◽  
Author(s):  
Jennifer Jury ◽  
Nahid Ahmedzadeh ◽  
E. E. Daniel
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Sodium Nitroprusside ◽  
Vasoactive Intestinal Peptide ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Electrophysiological Studies ◽  
Esophageal Sphincter ◽  
Long Pulse ◽  
Sphincteric Muscle

This study provides mechanical and electrophysiological evidence to show that a metabolite of arginine, not vasoactive intestinal peptide (VIP), is the putative nonadrenergic noncholinergic (NANC) inhibitory mediator in canine and opossum lower esophageal sphincters (LES). Relaxations of spontaneous active tension by electrical field stimulation (FS) at parameters that induced tetrodotoxin (TTX)-sensitive responses were abolished by L-Nω-arginine methyl ester (L-NAME) at 10−4 M and restored by L-arginine (10−3 M) but not D-arginine (10−3 M). TTX-insensitive relaxations to 5-ms pulses were unaffected by L-NAME, L- or D-arginine. VIP (10−6 M) caused maximum relaxations of basal tension in both the opossum and canine LES. However these relaxations, unlike those from FS were unaffected by L-NAME. Methylene blue (5 × 10−5 M) increased basal tension of the LES in each species, and did not inhibit the relaxation to FS or VIP, but often increased the amplitudes of these responses due to the increase in basal tension. In parallel experiments NANC inhibition of body circular muscle from opossum esophagus was abolished by methylene blue. Electrophysiological studies using micro-electrodes revealed that NANC inhibition was associated with inhibitory junction potentials in the canine LES. These were inhibited by L-NAME and restored by L-arginine but not D-arginine. In contrast, 10−6 M VIP in canine LES did not induce any change in membrane potential during a 20-min superfusion. Sodium nitroprusside also hyperpolarized sphincteric muscle and its effects were not affected by L-NAME. We conclude that esophageal sphincter NANC nerve initiation of inhibitory junction potentials or relaxations depend on a mediator produced from L-arginine, like those of esophageal body circular muscle. This mediator resembles sodium nitroprusside in its actions. However, either the NANC mediator or the response to it differs in body circular muscle and LES since only the former was clearly sensitive to methylene blue. Moreover, TTX-insensitive relaxations to long pulse durations were not mediated by nitric oxide-related mechanisms because L-NAME had no effect on them.Key words: nitric oxide, vasoactive intestinal peptide, sphincter relaxation, inhibitory junction potentials.

Functional difference between SP and NKA: relaxation of gastric muscle by SP is mediated by VIP and NO

1993 ◽  
Vol 264 (4) ◽  
pp. G678-G685
Author(s):  
J. G. Jin ◽  
S. Misra ◽  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
No Synthase ◽  
No Production ◽  
Neurokinin A ◽  
Functional Difference ◽  
Receptor Agonists ◽  
Gastric Muscle ◽  
Guinea Pig Stomach ◽  
Synthase Inhibitor

The mechanism of action of endogenous tachykinins [substance P (SP) and neurokinin A and B (NKA and NKB)] and of receptor-specific tachykinin analogues (SP methyl ester (SPME), [beta-Ala8]NKA-(4-10), and senktide) was examined in circular muscle of guinea pig stomach. Cross-desensitization studies confirmed that SPME and SP interacted with NK-1 receptors, [beta-Ala8]NKA-(4-10) and NKA with NK-2 receptors, and senktide and NKB with NK-3 receptors. NK-1 and NK-3-receptor agonists induced relaxation and stimulated vasoactive intestinal peptide (VIP) release and nitric oxide (NO) production: tetrodotoxin abolished VIP release, NO production, and relaxation, converting the response to NK-1-receptor agonists to contraction; the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) abolished NO production, partly inhibited VIP release (56-64%, P < 0.01), and abolished relaxation; the VIP antagonist VIP-(10-28) partly inhibited NO production (73-74%, P < 0.001) and relaxation (56-58%, P < 0.01); and atropine augmented relaxation by 28-35% (P < 0.01). The pattern of inhibition implied that: 1) relaxation was mediated by VIP and NO; 2) VIP release was partly dependent on NO production, since it was strongly inhibited by L-NNA; and 3) NO was largely produced by the action of VIP on muscle cells, since it was strongly inhibited by VIP-(10-28). NK-2-receptor agonists elicited only contraction that was not affected by tetrodotoxin; these agonists also inhibited VIP release, NO production, and relaxation induced by NK-1- and NK-3-receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural regulation of in vitro giant contractions in the rat colon

2001 ◽  
Vol 281 (1) ◽  
pp. G275-G282 ◽  
Author(s):  
Asensio Gonzalez ◽  
Sushil K. Sarna
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Sch 23390 ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Cells ◽  
Enteric Neurons ◽  
Rat Colon ◽  
Spontaneous Contractions

The rat middle colon spontaneously generates regularly occurring giant contractions (GCs) in vitro. We investigated the neurohumoral and intracellular regulation of these contractions in a standard muscle bath. cGMP content was measured in strips and single smooth muscle cells. The circular muscle strips generated spontaneous GCs. Their amplitude and frequency were significantly increased by tetrodotoxin (TTX), ω-conotoxin, N ω-nitro-l-arginine (l-NNA), and the dopamine D1 receptor antagonist Sch-23390. The GCs were unaffected by hexamethonium, atropine, and antagonists of serotonergic (5-HT1–4), histaminergic (H1–2), and tachykininergic (NK1–2) receptors but enhanced by NK3receptor antagonism. The guanylate cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ) also enhanced GCs to the same extent as TTX and l-NNA, and each of the three agents prevented the effects of the others. GCs were abolished by electrical field stimulation, S-nitroso- N-acetyl-penicillamine, and 8-bromo-cGMP. BAY-K-8644 and apamin enhanced the GCs, but they were abolished by D-600. Basal cGMP content in strips was decreased by TTX,l-NNA, or ODQ, but these treatments had no effect on cGMP content of enzymatically dissociated single smooth muscle cells. We conclude that spontaneous contractions in the rat colonic muscle strips are not generated by cholinergic, serotonergic, or histaminergic input. Constitutive release of nitric oxide from enteric neurons sustains cGMP synthesis in the colonic smooth muscle to suppress spontaneous in vitro GCs.

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.

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