Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1267-1272
Published online before print May 23, 2002, doi: 10.1161/01.ATV.0000023438.32585.A1
Published online before print May 23, 2002, doi: 10.1161/01.ATV.0000023438.32585.A1
© 2002 American Heart Association, Inc.
Vascular Biology |
Cholesterol Depletion Disrupts Caveolae and Differentially Impairs Agonist-Induced Arterial Contraction
From the Department of Physiological Sciences (K.D., P.H., K.S.), Lund University, Lund, Sweden, and the Department of Medical Physiology (M.V., J.V.) and the Department of Medical Anatomy (J.T.-J.), Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Correspondence to Dr Karl Swärd, Department of Physiological Sciences, Lund University, BMC F12, S-221 84 Lund, Sweden. E-mail karl.sward{at}mphy.lu.se
Objective— This study assessed the role of cholesterol-rich membrane regions, including caveolae, in the regulation of arterial contractility.
Methods and Results— Rat tail artery devoid of endothelium was treated with the cholesterol acceptor methyl-ß-cyclodextrin, and the effects on force and Ca2+ handling were evaluated. In cholesterol-depleted preparations, the force responses to 
1-adrenergic receptors, membrane depolarization, inhibition of myosin light chain phosphatase, and activation of G proteins with a mixture of 20 mmol/L NaF and 60 µmol/L AlCl3 were unaffected. In contrast, responses to 5-hydroxytryptamine (5-HT), vasopressin, and endothelin were reduced by >50%. The rise in global intracellular free Ca2+ concentration in response to 5-HT was attenuated, as was the generation of Ca2+ waves at the cellular level. By electron microscopy, cholesterol depletion was found to disrupt caveolae. The 5-HT response could be restored by exogenous cholesterol, which also restored caveolae. Western blots showed that the levels of 5-HT2A receptor and of caveolin-1 were unaffected by cholesterol extraction. Sucrose gradient centrifugation showed enrichment of 5-HT2A receptors, but not 1-adrenergic receptors, in the caveolin-1–containing fractions, suggesting localization of the former to caveolae.
Conclusions— These results show that a subset of signaling pathways that regulate smooth muscle contraction depends specifically on cholesterol. Furthermore, the cholesterol-dependent step in serotonergic signaling occurs early in the pathway and depends on the integrity of caveolae.
Key Words: smooth muscle • caveolae • 5-hydroxytryptamine • endothelin • intracellular calcium
This article has been cited by other articles:
 |
|
 |
|
  C. J. Clarke, S. Forman, J. Pritchett, V. Ohanian, and J. Ohanian Phospholipase C-{delta}1 modulates sustained contraction of rat mesenteric small arteries in response to noradrenaline, but not endothelin-1 Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H826 - H834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Morris, B. Lei, Y.-X. Wu, G. A. Michelotti, and D. A. Schwinn The {alpha}1a-Adrenergic Receptor Occupies Membrane Rafts with Its G Protein Effectors but Internalizes via Clathrin-coated Pits J. Biol. Chem., February 1, 2008; 283(5): 2973 - 2985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Halayko, T. Tran, and R. Gosens Phenotype and Functional Plasticity of Airway Smooth Muscle: Role of Caveolae and Caveolins Proceedings of the ATS, January 1, 2008; 5(1): 80 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Rodrigues, C. B. Restini, C. N. Lunardi, J. E. Moreira, R. G. Lima, R. S. da Silva, and L. M. Bendhack Caveolae Dysfunction Contributes to Impaired Relaxation Induced by Nitric Oxide Donor in Aorta from Renal Hypertensive Rats J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 831 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gosens, G. L. Stelmack, G. Dueck, M. M. Mutawe, M. Hinton, K. D. McNeill, A. Paulson, S. Dakshinamurti, W. T. Gerthoffer, J. A. Thliveris, et al. Caveolae facilitate muscarinic receptor-mediated intracellular Ca2+ mobilization and contraction in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1406 - L1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Albinsson, Y. Shakirova, A. Rippe, M. Baumgarten, B.-I. Rosengren, C. Rippe, R. Hallmann, P. Hellstrand, B. Rippe, and K. Sward Arterial remodeling and plasma volume expansion in caveolin-1-deficient mice Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1222 - R1231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Jie Zhang, A. Kendrick, S. Quenby, and S. Wray Contractility and Calcium Signaling of Human Myometrium Are Profoundly Affected by Cholesterol Manipulation: Implications for Labor? Reproductive Sciences, July 1, 2007; 14(5): 456 - 466. [Abstract] [PDF]
|
|
|
|
|
|
K. B. Atkins, A. Prezkop, J. L. Park, J. Saha, D. Duquaine, M. J. Charron, A. L. Olson, and F. C. Brosius 3rd Preserved expression of GLUT4 prevents enhanced agonist-induced vascular reactivity and MYPT1 phosphorylation in hypertensive mouse aorta Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H402 - H408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wray Insights into the uterus Exp Physiol, July 1, 2007; 92(4): 621 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Shmygol, K. Noble, and S. Wray Depletion of membrane cholesterol eliminates the Ca2+-activated component of outward potassium current and decreases membrane capacitance in rat uterine myocytes J. Physiol., June 1, 2007; 581(2): 445 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Clarke, V. Ohanian, and J. Ohanian Norepinephrine and endothelin activate diacylglycerol kinases in caveolae/rafts of rat mesenteric arteries: agonist-specific role of PI3-kinase Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2248 - H2256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tosun, Y. Erac, C. Selli, and N. Karakaya Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1961 - H1966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Adebiyi, G. Zhao, S. Y. Cheranov, A. Ahmed, and J. H. Jaggar Caveolin-1 abolishment attenuates the myogenic response in murine cerebral arteries Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1584 - H1592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mouzat, M. Prod'Homme, D. H. Volle, B. Sion, P. Dechelotte, K. Gauthier, J.-M. Vanacker, and J.-M. A. Lobaccaro Oxysterol Nuclear Receptor LXRbeta Regulates Cholesterol Homeostasis and Contractile Function in Mouse Uterus J. Biol. Chem., February 16, 2007; 282(7): 4693 - 4701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Dubroca, X. Loyer, K. Retailleau, G. Loirand, P. Pacaud, O. Feron, J.-L. Balligand, B. I. Levy, C. Heymes, and D. Henrion RhoA activation and interaction with Caveolin-1 are critical for pressure-induced myogenic tone in rat mesenteric resistance arteries Cardiovasc Res, January 1, 2007; 73(1): 190 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shakirova, J. Bonnevier, S. Albinsson, M. Adner, B. Rippe, J. Broman, A. Arner, and K. Sward Increased Rho activation and PKC-mediated smooth muscle contractility in the absence of caveolin-1. Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1326 - C1335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, W. R. Thelin, B. Yang, S. L. Milgram, and K. Jacobson Transient anchorage of cross-linked glycosyl-phosphatidylinositol-anchored proteins depends on cholesterol, Src family kinases, caveolin, and phosphoinositides J. Cell Biol., October 9, 2006; 175(1): 169 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Hassan, T. M. Williams, P. G. Frank, and M. P. Lisanti Caveolin-1-deficient aortic smooth muscle cells show cell autonomous abnormalities in proliferation, migration, and endothelin-based signal transduction Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2393 - H2401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Linder, R. Leite, K. Lauria, T. M. Mills, and R. C. Webb Penile erection requires association of soluble guanylyl cyclase with endothelial caveolin-1 in rat corpus cavernosum Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1302 - R1308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Hardin and J. Vallejo Caveolins in vascular smooth muscle: Form organizing function Cardiovasc Res, March 1, 2006; 69(4): 808 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Shaw, M. A. Sweeney, S. C. O'Neill, C. J.P. Jones, C. Austin, and M. J. Taggart Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of pressurised arteries: The relevance for Ca2+ oscillations and tone Cardiovasc Res, March 1, 2006; 69(4): 825 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vial and R. J. Evans Disruption of Lipid Rafts Inhibits P2X1 Receptor-mediated Currents and Arterial Vasoconstriction J. Biol. Chem., September 2, 2005; 280(35): 30705 - 30711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-R. Yang, M.-J. Lin, K.-P. Yip, L. H. Jeyakumar, S. Fleischer, G. P. H. Leung, and J. S. K. Sham Multiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated Ca2+ stores in pulmonary arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L338 - L348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Linder, L. P. McCluskey, K. R. Cole III, K. M. Lanning, and R. C. Webb Dynamic Association of Nitric Oxide Downstream Signaling Molecules with Endothelial Caveolin-1 in Rat Aorta J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 9 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Ratz, K. M. Berg, N. H. Urban, and A. S. Miner Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus Am J Physiol Cell Physiol, April 1, 2005; 288(4): C769 - C783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Venugopal, K. Hanashiro, Z.-Z. Yang, and Y. Nagamine Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes PNAS, December 7, 2004; 101(49): 17120 - 17125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Sampson, Y. Hayabuchi, N. B. Standen, and C. Dart Caveolae Localize Protein Kinase A Signaling to Arterial ATP-Sensitive Potassium Channels Circ. Res., November 12, 2004; 95(10): 1012 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bhatnagar, D. J. Sheffler, W. K. Kroeze, B. Compton-Toth, and B. L. Roth Caveolin-1 Interacts with 5-HT2A Serotonin Receptors and Profoundly Modulates the Signaling of Selected G{alpha}q-coupled Protein Receptors J. Biol. Chem., August 13, 2004; 279(33): 34614 - 34623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Daniel, G. Bodie, M. Mannarino, G. Boddy, and W.-J. Cho Changes in membrane cholesterol affect caveolin-1 localization and ICC-pacing in mouse jejunum Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G202 - G210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-D. Je, C. Gallant, P. C. Leavis, and K. G. Morgan Caveolin-1 regulates contractility in differentiated vascular smooth muscle Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H91 - H98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bergdahl, M. F. Gomez, K. Dreja, S.-Z. Xu, M. Adner, D. J. Beech, J. Broman, P. Hellstrand, and K. Sward Cholesterol Depletion Impairs Vascular Reactivity to Endothelin-1 by Reducing Store-Operated Ca2+ Entry Dependent on TRPC1 Circ. Res., October 31, 2003; 93(9): 839 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zeidan, J. Broman, P. Hellstrand, and K. Sward Cholesterol Dependence of Vascular ERK1/2 Activation and Growth in Response to Stretch: Role of Endothelin-1 Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1528 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Pike Lipid rafts: bringing order to chaos J. Lipid Res., April 1, 2003; 44(4): 655 - 667. [Abstract] [Full Text] [PDF]
|
|