Penile erection requires association of soluble guanylyl cyclase with endothelial caveolin-1 in rat corpus cavernosum

A. Elizabeth Linder, Romulo Leite, Kimberly Lauria, Thomas M. Mills, R Clinton Webb

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Erectile dysfunction is caused by a variety of pathogenic factors, particularly impaired formation and action of nitric oxide (NO). NO released from nerve endings and corpus cavernosum endothelial cells plays a crucial role in initiating and maintaining increased intracavernous pressure, penile vasodilatation, and penile erection. Classically, these effects are dependent on cGMP synthesized during activation of soluble guanylyl cyclase (sGC) by NO in smooth muscle cells. The enzyme NO synthase in endothelial cells has been localized to caveolae, small invaginations of the plasma membrane rich in cholesterol. Membrane cholesterol depletion impairs acetylcholine-induced relaxation in arteries attributed to an alteration in caveolar structure. It has been shown that sGC may be activated in endothelial caveolae contributing to vasodilation. We hypothesized that caveolae are the platform for sGC/cGMP signaling in cavernosum smooth muscle eliciting erection. Methyl-β- cyclodextrin, a pharmacological tool to deplete membrane cholesterol and disassemble caveolae, impaired rat erectile responses in vivo and cavernosum smooth muscle relaxation induced by the NO donor sodium nitroprusside and the sGC activator 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole in vitro. Methyl-β-cyclodextrin had no effect on cavernosum smooth muscle relaxation induced by NO released upon nerve stimulation or by exogenous cGMP. Furthermore, sGC and caveolin-1, the major coat protein of caveolae, were colocalized in rat corpus cavernosum sinusoidal endothelium. Electron microscopy indicated caveolae disruption in corpus cavernosum treated with methyl-β-cyclodextrin. In summary, our results provide evidence of compartmentalization of sGC in the caveolae of cavernosal endothelial cells contributing to NO signaling mediating smooth muscle relaxation and erection.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume290
Issue number5
DOIs
StatePublished - May 1 2006

Fingerprint

Penile Erection
Caveolin 1
Caveolae
Nitric Oxide
Muscle Relaxation
Smooth Muscle
Cyclodextrins
Endothelial Cells
Cholesterol
Vasodilation
Indazoles
Membranes
Nerve Endings
Nitric Oxide Donors
Capsid Proteins
Nitroprusside
Erectile Dysfunction
Soluble Guanylyl Cyclase
Nitric Oxide Synthase
Acetylcholine

Keywords

  • Caveolae
  • Nitric oxide
  • Relaxation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Penile erection requires association of soluble guanylyl cyclase with endothelial caveolin-1 in rat corpus cavernosum. / Linder, A. Elizabeth; Leite, Romulo; Lauria, Kimberly; Mills, Thomas M.; Webb, R Clinton.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 290, No. 5, 01.05.2006.

Research output: Contribution to journalArticle

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