Effects of a nitric oxide synthase inhibitor on non-cholinergic junction potentials in the circular muscle of the guinea pig ileum

Lyster, D. J. K.; Bywater, Robert A.R.; Taylor, Grahame S.; Watson, Michael J.

doi:10.1016/0165-1838(92)90058-o

Cited by 48 publications

(37 citation statements)

References 16 publications

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“…26,29,30,33,34 The antiperistaltic action of STX-6c was analyzed with respect to the possibility that this ET B receptor agonist depresses peristalsis via activation of inhibitory motor neurons, which in the guinea pig intestine relax the muscle primarily via release of NO, ATP, vasoactive intestinal polypeptide, and/or pituitary adenylate cyclaseactivating peptide. [35][36][37][38] However, peristaltic motor inhibition caused by STX-6c remained unaltered by an effective concentration (300 µmol/L) of the NO synthase inhibitor L-NAME, 25,39 which is in line with a lack of NO involvement in ET-induced suppression of intestinal muscle contractility. 11,13 Effective concentrations of the P2X purinoceptor antagonist PPADS, which antagonizes the antiperistaltic action of endogenously released ATP, 27,40 and of the opioid receptor antagonist naloxone 26 were likewise unable to prevent STX-6c from inhibiting peristalsis.…”

Section: Discussionmentioning

confidence: 71%

Regulation of Guinea pig intestinal peristalsis by endogenous endothelin acting at ETB receptors

Shahbazian

Holzer

2000

Gastroenterology

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Section: Discussionmentioning

confidence: 71%

Regulation of Guinea pig intestinal peristalsis by endogenous endothelin acting at ETB receptors

Shahbazian

Holzer

2000

Gastroenterology

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“…On the other hand, the apaminresistant ij.p. has been reported to be associated with little change in membrane conductance (Lyster et al, 1992), an increase in the membrane K+ conductance (Jury et al, 1985;Christinck et al, 1990;Kitamura et al, 1993), or with a decreased Cl-conductance (Crist et al, 1991). In the present experiments, we examine the nature of the membrane conductance changes underlying the hyperpolarizations and rebound PSDs of the circular muscle of the guinea-pig proximal colon induced by the NO donors, NO, NC and SNP.…”

Section: Introductionmentioning

confidence: 99%

Effects of nitric oxide (NO) and NO donors on the membrane conductance of circular smooth muscle cells of the guinea‐pig proximal colon

Watson

Bywater

Taylor

et al. 1996

British J Pharmacology

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1 The membrane conductance changes underlying the membrane hyperpolarizations induced by nitric oxide (NO), S-nitroso-L-cysteine (NC) and sodium nitroprusside (SNP) were investigated in the circular smooth muscle cells of the guinea-pig proximal colon, by use of standard intracellular microelectrode recording techniques.2 NO (1%), NC (2.5-25 AM) and SNP (1-1000 FM) induced membrane hyperpolarization in a concentration-dependent manner, the hyperpolarizations to NO and NC developing more rapidly than those to SNP. The slower-developing responses to SNP were mimicked by the membrane permeable analogue of guanosine 3':5' cyclic-monophosphate (cyclic GMP), 8-bromo-cyclic GMP (500 AM), and by isoprenaline (10 AM).3 The hyperpolarizations to NC and SNP were reduced in a low Ca2" (0.25 mM) saline and upon the addition of haemoglobin (20 AM), but were not effected by NG-nitro-L-arginine (L-NOARG) (100 AM) or cw-conotoxin GVIA (100 nM). The hyperpolarizations to SNP were also significantly reduced by methylene blue (50 AM). However, TEA (5-15 mm) reduced the membrane hyperpolarizations to SNP (10 AM) and isoprenaline (10 AM) in a concentration-dependent manner. The hyperpolarization to isoprenaline (10 AM) remaining in the presence of 15 mm TEA was blocked by ouabain (10 M). 5 The amplitude of electrotonic potentials (1 s duration) elicited during NO donor hyperpolarizations were little changed or only slightly reduced (5-25%). However, the amplitude of the electrotonic potentials elicited during maintained electrically-induced hyperpolarizations of similar amplitude were significantly increased (30-150%), suggesting that the non-linear membrane properties of the proximal colon partially mask an increase in membrane conductance elicited during the NO donor hyperpolarizations. 6 Membrane hyperpolarization in the presence of an NO donor, 8-bromo-cyclic GMP, isoprenaline, or upon application of a maintained hyperpolarizing electrical current, often evoked oscillations of the membrane potential. These oscillations were prevented by Cs' (1 mM). 7 These results indicate that NO and NC hyperpolarize the circular muscle of the proximal colon by activating at least two TEA-resistant membrane K+ conductances, one of which is sensitive to apamin blockade. The K+ conductance increases activated by SNP or 8-bromo-cyclic GMP were little effected by apamin, perhaps suggesting a common mechanism. In contrast, the hyperpolarization to isoprenaline appears to involve the activation of TEA-sensitive Ca2+-activated K+ ('BK') channels, as well as a Na:K ATPase. Finally, the 'background' membrane conductance of the circular muscle cells of the proximal colon decreased upon membrane hyperpolarization to reveal oscillations of the membrane potential which may well represent 'pacemaker' or 'slow wave' activity.

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“…Recently, the presence of nitric oxide synthase has been demonstrated in the enteric inhibitory motoneurons to the circular muscle ) and nitric oxide has been shown to mediate apamin-resistant transmission from these neurons. Analogues of L-arginine which inhibit the synthetic enzyme for nitric oxide block slow inhibitory junction potentials (Lyster, Bywater, Taylor & Watson, 1992) and apamin-resistant relaxation of the circular muscle layer (Humphreys, Costa & Brookes, 1991). A combination of apamin and an arginine analogue blocks the relaxation mediated by enteric inhibitory motoneurons (Humphreys et al 1991).…”

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confidence: 99%

The role of enteric inhibitory motoneurons in peristalsis in the isolated guinea‐pig small intestine.

Waterman

Costa

1994

The Journal of Physiology

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1. Peristalsis is a co-ordinated motor behaviour in which an anally propagated contraction of the circular muscle propels intraluminal contents. The role of excitatory motoneurons in peristalsis is well established; however the role of enteric inhibitory motoneurons is unknown. 2. A combination of a nitric oxide synthase inhibitor and apamin, which blocks relaxation of the circular muscle of guinea-pig small intestine mediated by enteric inhibitory motoneurons, was used to investigate the role of inhibitory motoneurons in peristalsis in isolated segments of guinea-pig small intestine.3. Nd-nitro-L-arginine methyl ester (L-NAME, 400 /LM) and NW-nitro-L-arginine (L-NOArg, 100 ,UM) significantly reduced the threshold volume required to trigger emptying of the intestine. This effect was reversed by L-arginine (4 mM) and L-arginine alone increased the threshold volume for initiation of peristalsis. Sodium nitroprusside (0'1-10 ,sM), which generates nitric oxide, also increased the threshold volume. L-NAME, L-NOArg, L-arginine and sodium nitroprusside did not alter the maximal intraluminal pressure generated during emptying. Contraction of the longitudinal muscle during the initial phase of fluid infusion was significantly increased by L-NAME and L-NOArg and reduced by sodium nitroprusside (1 nM to 10/tM).4. Apamin (0 5 ,1M) did not significantly alter the threshold volume necessary to initiate peristalsis or contraction of the longitudinal muscle. However, the maximal pressure generated when the intestine was emptying was significantly increased. Furthermore, short segments of circular muscle contracted apparently randomly, before peristaltic emptying was triggered. 5. A combination of L-NAME and apamin completely disrupted peristalsis. Contractions of the circular muscle did not always start at the oral end. Stationary contractions as well as contractions propagating orally and anally were observed. 6. It is concluded that enteric inhibitory motoneurons are crucial for peristalsis to occur.They are important in setting the threshold at which peristaltic emptying is triggered, via nitric oxide. They are essential for the propagation of the circular muscle contraction, via an apamin-sensitive mechanism of transmission. Contraction of the longitudinal muscle during peristalsis is partly inhibited by a nitric oxide-mediated mechanism.

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Effects of a nitric oxide synthase inhibitor on non-cholinergic junction potentials in the circular muscle of the guinea pig ileum

Cited by 48 publications

References 16 publications

Regulation of Guinea pig intestinal peristalsis by endogenous endothelin acting at ETB receptors

Regulation of Guinea pig intestinal peristalsis by endogenous endothelin acting at ETB receptors

Effects of nitric oxide (NO) and NO donors on the membrane conductance of circular smooth muscle cells of the guinea‐pig proximal colon

The role of enteric inhibitory motoneurons in peristalsis in the isolated guinea‐pig small intestine.

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