nNOS in canine lower esophageal sphincter: colocalized with Cav-1 and Ca<sup>2+</sup>-handling proteins?

Daniel, E. E.; Jury, Jennifer; Wang, Y. F.

doi:10.1152/ajpgi.2001.281.4.g1101

Cited by 37 publications

(44 citation statements)

References 50 publications

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“…Cav-3 is also expressed in gastrointestinal smooth muscle although its expression is less abundant than Cav-1. The role of Cav-3 is unknown relative to Cav-1 and PDE5 (7,10,30,47). It is possible that Cav-3 can subserve some of the roles of Cav-1 at a reduced level in the absence of Cav-1.…”

Section: Resultsmentioning

confidence: 99%

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion

Mahavadi

Bhattacharya²,

Kumar³

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Murthy KS. Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1 Ϫ/Ϫ mice impair the peristaltic reflex and propulsion. Am J Physiol Gastrointest Liver Physiol 305: G964 -G974, 2013. First published October 24, 2013 doi:10.1152/ajpgi.00165.2013.-Caveolae are specialized regions of the plasma membrane that concentrate receptors and associated signaling molecules critical in regulation of cellular response to transmitters and hormones. We have determined the effects of caveolin-1 (Cav-1) deletion, caveolin-1 siRNA, and caveolar disruption in mice on the signaling pathways that mediate contraction and relaxation in colonic smooth muscle and on the components of the peristaltic reflex in isolated tissue and propulsion in intact colonic segments. In Cav-1 Ϫ/Ϫ mice, both relaxation and contraction were decreased in smooth muscle cells and muscle strips, as well as during both phases of the peristaltic reflex and colonic propulsion. The decrease in relaxation in response to the nitric oxide (NO) donor was accompanied by a decrease in cGMP levels and an increase in phosphodiesterase 5 (PDE5) activity. Relaxation by a PDE5-resistant cGMP analog was not affected in smooth muscle of Cav-1 Ϫ/Ϫ mice, suggesting that inhibition of relaxation was due to augmentation of PDE5 activity. Similar effects on relaxation, PDE5 and cGMP were obtained in muscle cells upon disruption of caveolae by methyl-␤-cyclodextrin or suppression of Cav-1. Sustained contraction mediated via inhibition of myosin light chain phosphatase (MLCP) activity is regulated by Rho kinase and PKC via phosphorylation of two endogenous inhibitors of MLCP: myosin phosphatasetargeting subunit (MYPT1) and 17-kDa PKC-potentiated protein phosphatase 1 inhibitor protein (CPI-17), respectively. The activity of both enzymes and phosphorylation of MYPT1 and CPI-17 were decreased in smooth muscle from Cav-1 Ϫ/Ϫ mice. We conclude that the integrity of caveolae is essential for contractile and relaxant activity in colonic smooth muscle and the maintenance of neuromuscular function at organ level.caveolin; phosphodiesterase; Rho kinase; smooth muscle; peristaltic reflex CAVEOLAE AND THEIR MAIN MEMBRANE PROTEINS, caveolin-1 (Cav-1), -2, and -3, form regular invaginations of the plasma membrane, which are sites that concentrate receptors, G proteins, effector enzymes, and associated signaling molecules in several cell types (reviewed in Refs. 2, 4, 22, 37, 50). As such, they play a critical role in regulating, either by augmenting or inhibiting, the physiological response of cells to transmitters and hormones. Most studies have concentrated on identifying their role in regulating the response to agonists at the cellular level; however, the translation of these cellular effects of caveolin to the organ level is less well understood although many roles have been postulated (1, 25, 43-45, 50, 58).In the gut, caveoli are present on many cell types, including smooth muscle cells, interstitial cells of Cajal (ICC), and endothelial cell...

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Section: Resultsmentioning

confidence: 99%

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion

Mahavadi

Bhattacharya²,

Kumar³

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Mechanism of hSlo1 and Caveolin-1 Association-Positive evidence for a functional correlation or association between Slo1 and caveolin-1 has been observed in other tissues (5,(13)(14)(15)26). Pull-down experiments using glutathione S-transferase-caveolin-1 protein, and lysates of HEK293T cells expressing hSlo1 indicate that these two proteins can associate; however, an indirect binding cannot be ruled out (14).…”

Section: Association Of Slo1 Protein With Caveolin-1 In Native Aorticmentioning

confidence: 99%

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Alioua¹,

Lü²,

Kumar³

et al. 2008

Journal of Biological Chemistry

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The large conductance, voltage-and Ca 2؉ -activated potassium (MaxiK, BK) channel and caveolin-1 play important roles in regulating vascular contractility. Here, we hypothesized that the MaxiK ␣-subunit (Slo1) and caveolin-1 may interact with each other. Slo1 and caveolin-1 physiological association in native vascular tissue is strongly supported by (i) detergent-free purification of caveolin-1-rich domains demonstrating a pool of aortic Slo1 co-migrating with caveolin-1 to light density sucrose fractions, (ii) reverse co-immunoprecipitation, and (iii) double immunolabeling of freshly isolated myocytes revealing caveolin-1 and Slo1 proximity at the plasmalemma. In HEK293T cells, Slo1-caveolin-1 association was unaffected by the smooth muscle MaxiK ␤1-subunit. Sequence analysis revealed two potential caveolin-binding motifs along the Slo1 C terminus, one equivalent, 1007 YNMLCFGIY 1015 , and another mirror image, 537 YT-EYLSSAF 545 , to the consensus sequence, XXXX XX . Deletion of 1007 YNMLCFGIY 1015 caused ϳ80% loss of Slo1-caveolin-1 association while preserving channel normal folding and overall Slo1 and caveolin-1 intracellular distribution patterns. 537 YTEYLSSAF 545 deletion had an insignificant dissociative effect. Interestingly, caveolin-1 coexpression reduced Slo1 surface and functional expression near 70% without affecting channel voltage sensitivity, and deletion of 1007 YNMLCF-GIY 1015 motif obliterated channel surface expression. The results suggest 1007 YNMLCFGIY 1015 possible participation in Slo1 plasmalemmal targeting and demonstrate its role as a main mechanism for caveolin-1 association with Slo1 potentially serving a dual role: (i) maintaining channels in intracellular compartments downsizing their surface expression and/or (ii) serving as anchor of plasma membrane resident channels to caveolin-1-rich membranes. Because the caveolin-1 scaffolding domain is juxtamembrane, it is tempting to suggest that Slo1-caveolin-1 interaction facilitates the tethering of the Slo1 C-terminal end to the membrane.Large conductance, voltage-and Ca 2ϩ -activated potassium (MaxiK, BK) 4 channels play important roles in vascular, neuronal, and urinary functions. In vascular smooth muscle, MaxiK channel appears to be a unique signaling protein because of its ability to mediate the effects of several vasoconstricting as well as vasodilating agents. The ability of MaxiK protein to complete with high fidelity these opposite tasks calls for specific associations and subcellular compartmentalization with corresponding signaling partners (1). Recently, it has been appreciated that many signaling molecules are segregated primarily in specialized microdomains like caveolae (plasma membrane invaginations enriched with cholesterol and caveolin protein), thereby, optimizing signal transduction between agonists and specific effectors (2).Three caveolin proteins have been identified, caveolin-1, -2, and -3. All of them seem to be expressed in smooth muscle (3, 4). However, gene ablation experiments have shown that caveolin-1 p...

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“…Ϫ/Ϫ mice with anti-cav3 antibody and the antibody for nNOS-C, which recognizes the myogenic variant of nNOS (12), showed that cav3 immunoreactivity was found in the periphery of smooth muscle cells in the outer CM layer in both control and Cav1 Ϫ/Ϫ tissue (Fig. 2, b and e).…”

Section: Immunohistochemical Studiesmentioning

confidence: 89%

“…Cav1, -2, and -3 are a family of integral membrane proteins (21)(22)(23)(24) that are the principal components of the caveolar membrane in vivo (8,39). In smooth muscle and interstitial cells of Cajal (ICC), the most important caveolin is cav1 (12,14). They form homo-and heterooligomers that insert in the inner leaflet of plasma membrane to form the characteristic flask-shaped caveolae (47).…”

mentioning

confidence: 99%

Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles

El-Yazbi

Cho

Boddy

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles. Am J Physiol Gastrointest Liver Physiol 290: G394 -G403, 2006. First published September 15, 2005 doi:10.1152/ajpgi.00321.2005.-Recently, we showed that caveolin-1 (cav1) knockout mice (Cav1 Ϫ/Ϫ mice) have impaired nitric oxide (NO) function in the longitudinal muscle (LM) layer of the small intestine. The defect was a reduced responsiveness of the muscles to NO compensated by an increase in the function of apamin-sensitive, nonadrenergic, noncholinergic (NANC) mediators. In the present study, we examined similarly the effects of cav1 knockout on the relaxation in circular muscle (CM) of the mouse small intestine. CM of Cav1Ϫ/Ϫ mice also showed defective NO function, but less than in LM, as well as more activation of apamin-sensitive NANC mediators. CM of Cav1Ϫ/Ϫ mice, like LM, lacked cav1 but retained small amounts of cav3 and caveolae in the outer CM layer. In addition, we also examined the effects of a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-␣]quinazolin-1-one (ODQ), on electric field stimulation (EFS)-mediated relaxation in both LM and CM. ODQ had an effect similar to the block of NO synthesis. Moreover, we compared the actions of two NO donors in the LM and CM of control and Cav1 Ϫ/Ϫ mice. Similar to LM, CM of Cav1 Ϫ/Ϫ mice showed a reduced responsiveness to the NO donors sodium nitroprusside and S-nitroso-N-acetyl penicillamine. However, both ODQ and apamin blocked the inhibitory effects of the NO donors in LM, whereas apamin had no effect in CM. In conclusion, cav1 knockout affects NO function in both LM and CM, but its effects in CM differ significantly.

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nNOS in canine lower esophageal sphincter: colocalized with Cav-1 and Ca²⁺-handling proteins?

Cited by 37 publications

References 50 publications

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles

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nNOS in canine lower esophageal sphincter: colocalized with Cav-1 and Ca2+-handling proteins?

Cited by 37 publications

References 50 publications

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1−/− mice impair the peristaltic reflex and propulsion

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1−/− mice impair the peristaltic reflex and propulsion

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles

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Product

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nNOS in canine lower esophageal sphincter: colocalized with Cav-1 and Ca²⁺-handling proteins?

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion