Myogenic nitric oxide synthase activity in canine lower oesophageal sphincter: morphological and functional evidence

Salapatek, Anne Marie; Mao, Yu; Lam, Annette; Daniel, E. E.

doi:10.1038/sj.bjp.0701701

Cited by 27 publications

(33 citation statements)

References 43 publications

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“…1, 2, and 3, B and C). Tetrodotoxin alone or combined with -conotoxin (GVIA) had no effect on tone (Salapatek et al, 1998b). When tetrodotoxin had blocked responses to electrical field stimulation, TEA, but not ODQ, still increased active tone (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Previously we showed that canine LES contains a membrane-bound, constitutive nitric-oxide synthase (Salapatek et al, 1998b,c) that acts to limit development of tone in canine LES. This nitric-oxide synthase, which appears to be neural (Daniel et al, 2001a), uses Ca 2ϩ entering through nearby L-type calcium channels for activation and tone regulation by NO formation that activates K ϩ channels, including BK Ca channels .…”

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confidence: 99%

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Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter

Daniel

Bowes²,

Jury³

2002

J Pharmacol Exp Ther

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Whether cGMP and cytosolic guanylate cyclase (cGC) mediate responses of canine lower esophageal sphincter (LES) to nitric oxide (NO) released from nerves, produced in muscle, or added exogenously was evaluated in vitro. 1-H-(1,2,4)oxadiazole(4,3-␣)quinoxalin-1-1 (ODQ), inhibitor of cGC, reduced relaxations to nerve stimulation and sodium nitroprusside but not to nitricoxide synthase activity-dependent outward K ϩ -currents in isolated muscle cells. ODQ also failed to increase tone after nerve blockade. Nonspecific K ϩ channel blocker, TEA ion at 20 mM was previously shown to increase tone, occlude NO-mediated modulation of tone, and inhibit NO-dependent outward currents but not neural relaxation in LES cells . In this study, TEA abolished neural relaxation and nearly abolished relaxation to sodium nitroprusside when present with ODQ. We conclude that mechanisms coupling NO in canine LES to responses vary with the source of NO. ODQ-dependent mechanisms, presumably involving cGC, mediate actions of NO from nerves, but NO from muscle utilizes TEA-sensitive but not ODQ-dependent mechanisms to modulate tone and outward currents. Exogenous NO utilizes both TEA-and ODQ-dependent mechanisms.

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Section: Resultsmentioning

confidence: 97%

mentioning

confidence: 99%

Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter

Daniel

Bowes²,

Jury³

2002

J Pharmacol Exp Ther

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“…Ca 2+ entering through L-type Ca 2+ channels may activate this NOS to release NO, which in turn activates BK Ca channels to limit contraction. In earlier studies in canine LES, we showed that a similar myogenic nNOS existed associated with caveolin 1 [29,30]. Its role was to limit spontaneous myogenic tone by releasing NO continually in response to Ca 2+ entering through VDCC to activate BK Ca channels.…”

Section: Functional Experimentsmentioning

confidence: 99%

“…Functional studies of contraction have been carried out with intact strips segments of canine or small segments of mouse gastrointestinal tract and described in detail elsewhere [28][29][30][31][32][33]. In most cases, nerve functions were blocked with tetrodotoxin (10 M).…”

Section: Methodsmentioning

confidence: 99%

“…The authors attributed the loss of regulation of Ca 2+ sparks by voltage-dependent calcium channels to an increase in the distance between ryanodine and voltage-dependent calcium channels associated with the disappearance of caveolae [78]. In canine LES, NO released from myogenic nNOS modulated calcium entry by acting on BK Ca channels [29,30].…”

Section: Non-specific Cation Channelsmentioning

confidence: 99%

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Caveolae and calcium handling, a review and a hypothesis

Daniel

El‐Yazbi

Cho

2006

Journal of Cellular and Molecular Medicine

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Caveolae are associated with molecules crucial for calcium handling. This review considers the roles of caveolae in calcium handling for smooth muscle and interstitial cells of Cajal (ICC). Structural studies showed that the plasma membrane calcium pump (PMCA), a sodium-calcium exchanger (NCX1), and a myogenic nNOS appear to be colocalized with caveolin I, the main constituent of these caveolae. Voltage dependent calcium channels (VDCC) are associated but not co-localized with caveolin 1, as are proteins of the peripheral sarcoplasmic reticulum (SR) such as calreticulin. Only the nNOS is absent from caveolin 1 knockout animals. Functional studies in calcium free media sugest that a source of calcium in tonic smooth muscles exists, partly sequestered from extracellular EGTA. This source supported sustained contractions to carbachol using VDCC and dependent on activity of the SERCA pump. This source is postulated to be caveolae, near peripheral SR. New evidence, presented here, suggests that a similar source exists in phasic smooth muscle of the intestine and its ICC. These results suggest that caveolae and peripheral SR are a functional unit recycling calcium through VDCC and controlling its local concentration. Calcium handling molecules associated with caveolae in smooth muscle and ICC were identified and their possible functions also reviewed.

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Postnatal development of nitrergic neurons in the myenteric plexus of rat stomach

Timmermans¹,

Adriaensen²,

Lefebvre³

1999

Histochemistry and Cell Biology

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The effect of age on the proportion of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-positive neurons was investigated in the myenteric plexus of five different gastric areas of 1-day-, 1-week-, 2-week-, 1-month- and 2-month-old rats. Protein gene product 9.5 immunocytochemistry was used as a marker for the total enteric neuron population in order to establish the percentage of gastric nitrergic neurons in relation to age. The percentage of NADPHd-positive neurons in the proximal parts of the rat stomach (34-38%) is significantly higher than in the antral part (29%). This difference persists in all the age groups investigated. No significant relative increase with age of NADPHd-positive neurons could be observed in any of the areas studied. These findings imply that the increased nitrergic response in the rat proximal stomach as seen in pharmacological studies cannot be explained by an increased relative number of nitrergic neurons.

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Myogenic nitric oxide synthase activity in canine lower oesophageal sphincter: morphological and functional evidence

Cited by 27 publications

References 43 publications

Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter

Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter

Caveolae and calcium handling, a review and a hypothesis

Postnatal development of nitrergic neurons in the myenteric plexus of rat stomach

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