Characteristic features of inhibitory junction potentials evoked by single stimuli in the guinea‐pig isolated taenia caeci.

Bridgewater, Melissa; Cunnane, T.C.; Brading, Alison F.

doi:10.1113/jphysiol.1995.sp020719

Cited by 42 publications

(35 citation statements)

References 35 publications

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“…IJPs recorded from the rat colon showed two phases: a sharp decrease of the membrane potential (fast component) followed by a sustained hyperpolarization (slow component). This biphasic IJP is similar to those described in other preparations such as mouse colon (Shuttleworth et al, 1997), mouse ileum (Ward et al, 1994), guinea-pig taenia caeci (Bridgewater et al, 1995), guinea-pig ileum (Crist et al, 1992), human colon (Keef et al, 1993) and human jejunum (Stark et al, 1993), whereas a monophasic IJP has been recorded from the pig (Borderies et al, 1997) and dog (Stark et al, 1993) ileum. The presence of two components in the IJP may suggest a cotransmission.…”

Section: Discussionsupporting

confidence: 86%

“…However, it has become evident that IJPs may often show two phases, a fast and a slow hyperpolarization. Thus, this pro®le has been described for the IJP elicited by EFS of mouse colon (Shuttleworth et al, 1997), mouse ileum (Ward et al, 1994), guinea-pig taenia caeci (Bridgewater et al, 1995), guinea-pig ileum (Crist et al, 1992), human colon (Keef et al, 1993) and human jejunum (Stark et al, 1993). This biphasic shape of the IJP may suggest the release of more than one neurotransmitter.…”

Section: Introductionmentioning

confidence: 63%

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Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Plujà

Fernández

Jiménez

1999

British J Pharmacology

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1 The rat colonic circular muscle displays cyclic episodes of myenteric potential oscillations (MPOs), each of them associated with a spontaneous contraction. Nifedipine 1 mM abolished both MPOs and their associated contractions. TTX (1 mM) increased the amplitude and frequency of spontaneous contractions. 2 Electrical ®eld stimulation (EFS) induced a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (IJP), with two phases: an initial fast hyperpolarization (characterized by IJP amplitude) and a sustained hyperpolarization (characterized by IJP duration). 3 Sodium nitroprusside (10 mM) hyperpolarized and abolished spontaneous contractions even in presence of TTX or 1 mM apamin. ATP (100 mM) also hyperpolarized and abolished spontaneous contractions but its e ects were decreased by TTX and abolished by apamin. 4 Suramin (100 mM) or apamin reduced the amplitude of the IJPs, but did not a ect their duration. Incubation with L-NOARG (1 mM) reduced the duration but not the amplitude of the IJPs. In presence of L-NOARG plus suramin or L-NOARG plus apamin, both duration and amplitude of the IJPs were reduced but a residual IJP could still be recorded. 5 We conclude that the mechanical and electrical cyclic activity of the rat colonic circular muscle is modulated but not originated by the enteric nervous system and involves L-type calcium channel activity. EFS induces release of NANC inhibitory neurotransmitters which hyperpolarize and relax smooth muscle cells. Both ATP and NO are involved in IJP generation: ATP is responsible for the ®rst phase of the IJPs involving activation of apamin-sensitive potassium channels, whereas NO initiates the second phase which is independent of the activation of such channels.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 63%

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Plujà

Fernández

Jiménez

1999

British J Pharmacology

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“…-conotoxin GVIA also blocks purinergic IJPs (25). EFS-evoked release of ␤-NAD increased as a function of stimulation frequency.…”

Section: Resultsmentioning

confidence: 92%

“…Thus, a substantial portion of the ATP released could have been extrajunctional or could have resulted from stimulation of another population of neurons with -conotoxin-insensitive Ca 2ϩ entry pathways at nerve terminals (i.e., intrinsic nerves other than enteric inhibitory neurons or extrinsic nerves). Fast IJPs in gastrointestinal muscles are blocked by -conotoxin (25), and -conotoxin strongly inhibited the release of ␤-NAD (and its metabolites). Thus, it appears that a substantial fraction of the ␤-NAD released came from nerve terminals of enteric inhibitory nerves.…”

Section: Discussionmentioning

confidence: 99%

β-Nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle

Mutafova‐Yambolieva

Hwang

Hao

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

164

325

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Peripheral inhibitory nerves are physiological regulators of the contractile behavior of visceral smooth muscles. One of the transmitters responsible for inhibitory neurotransmission has been reputed to be a purine, possibly ATP. However, the exact identity of this substance has never been verified. Here we show that ␤-nicotinamide adenine dinucleotide (␤-NAD), an inhibitory neurotransmitter candidate, is released by stimulation of enteric nerves in gastrointestinal muscles, and the pharmacological profile of ␤-NAD mimics the endogenous neurotransmitter better than ATP. Levels of ␤-NAD in superfusates of muscles after nerve stimulation exceed ATP by at least 30-fold; unlike ATP, the release of ␤-NAD depends on the frequency of nerve stimulation. ␤-NAD is released from enteric neurons, and release was blocked by tetrodotoxin or -conotoxin GVIA. ␤-NAD is an agonist for P2Y1 receptors, as demonstrated by receptor-mediated responses in HEK293 cells expressing P2Y1 receptors. Exogenous ␤-NAD mimics the effects of the enteric inhibitory neurotransmitter. Responses to ␤-NAD and inhibitory junction potentials are blocked by the P2Y1-selective antagonist, MRS2179, and the nonselective P2 receptor antagonists, pyridoxal phosphate 6-azophenyl-2,4-disulfonic acid and suramin. Responses to ATP are not blocked by these P2Y receptor inhibitors. The expression of CD38 in gastrointestinal muscles, and specifically in interstitial cells of Cajal, provides a means of transmitter disposal after stimulation. ␤-NAD meets the traditional criteria for a neurotransmitter that contributes to enteric inhibitory regulation of visceral smooth muscles.enteric nervous system ͉ gastrointestinal motility ͉ P2Y receptor ͉ purinergic neurotransmission ͉ interstitial cells of Cajal

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“…In particular adenosine 5'-triphodifferent regions of the intestine (Costa et al, 1986; Manzini et sphate (ATP) (Burnstock et al, 1970;Burnstock, 1981;, and that different mechanisms regulate the release of Vladimirova & Shuba, 1984;Zagorodnyuk & Shuba, 1986; different NANC inhibitory transmitters (Zagorodnyuk & Crist et al, 1992). Vasoactive intestinal peptide (VIP) (Grider Maggi, 1994;Bridgewater et al, 1995). & Rivier, 1990;Crist et al, 1992) and, more recently, nitric…”

Section: Introductionmentioning

confidence: 99%

The possible role of ATP and PACAP as mediators of apamin‐sensitive NANC inhibitory junction potentials in circular muscle of guinea‐pig colon

Zagorodnyuk

Santicioli

Maggi

et al. 1996

British J Pharmacology

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Bogomoletz Institute of Physiology, Kiev, Ukraine 1 In the presence of atropine (1 gM), guanethidine (3 gM), indomethacin (3 Mm), nifedipine (1 MM), Lnitroarginine (L-NOARG, 100 pM), and the selective tachykinin NK, and NK2 receptor antagonists, SR 140,333 and GR 94,800, respectively (0.1 gM each), a single pulse of electrical field stimulation (EFS) produced a monophasic non-adrenergic non-cholinergic (NANC) inhibitory junction potential (ij.p., about 10 mV in amplitude) in the circular muscle of guinea-pig proximal colon, recorded by the modified single sucrose gap technique.2 The P2 purinoceptor agonist, a,# methylene ATP (cz,1 mATP, 100 gM) and the pituitary adenylyl cyclase activating peptide (PACAP, 1 gM) both produced hyperpolarization (11 + 0.8 mV, n = 14 and 10.2+0.8 mV, n= 19, respectively) and relaxation (1.1+0.2 mV, n= 14 and 1.5+0.2 mN, n= 19, respectively) of the circular muscle.3 Apamin (0.1 Mm) nearly abolished (about 90% inhibition) the NANC i.j.p. and the a,f3 mATPinduced hyperpolarization, markedly reduced the a,,B mATP-induced relaxation (73% inhibition) and the PACAP-induced hyperpolarization (65% inhibition), while the PACAP-induced relaxation was unaffected. 4 Tetraethylammonium (TEA, 10 mM) increased the EFS-evoked ij.p. and revealed an excitatory junction potential (ej.p.). In the presence of TEA, o,fl mATP induced a biphasic response: transient depolarization and contraction followed by hyperpolarization and relaxation. The hyperpolarization to PACAP was reduced by TEA (45% inhibition) but the relaxation was unaffected. 5 The combined application of apamin (0.1 Mm) and TEA (10 mM) abolished the ij.p. and single pulse EFS evoked a pure ej.p. with latency three times longer than that of the ij.p. In the majority of strips tested, a,,B mATP and PACAP elicited a biphasic response : depolarization and small contraction followed by hyperpolarization and relaxation. 6 The P2 purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) inhibited the NANC ij.p. in concentration-dependent manner and inhibited the a,f mATP-induced hyperpolarization and relaxation, without affecting the hyperpolarization and relaxation induced by PACAP. On the other hand, the P2 purinoceptor antagonist, suramin (100 gM) inhibited to a similar extent (60-80%) the NANC ij.p. and the hyperpolarization and relaxation induced by ci,fl mATP or PACAP. 7 PPADS and suramin reduced the NANC ej.p. evoked by a single pulse EFS in the presence of apamin and TEA (100 Mm of PPADS and 300 gM of suramin inhibited the ej.p. by about 40%).8 We conclude that ATP, but not PACAP, mediates the apamin-sensitive NANC ij.p. in the circular muscle of the guinea-pig colon. After blockade of the NANC ij.p., ATP may act as an excitatory transmitter by activating excitatory P2 purinoceptors. The subtypes of P2 purinoceptor involved in the inhibitory and excitatory responses remain to be established. The data suggest that excitatory P2 purinoceptors may be located extrajunctionally.

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Characteristic features of inhibitory junction potentials evoked by single stimuli in the guinea‐pig isolated taenia caeci.

Cited by 42 publications

References 35 publications

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

β-Nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle

The possible role of ATP and PACAP as mediators of apamin‐sensitive NANC inhibitory junction potentials in circular muscle of guinea‐pig colon

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