Ceram, a novel second messenger relaxes vascular smooth muscle

J. S. Jin, R Clinton Webb

Research output: Contribution to journalArticle

Abstract

Recent findings demonstrate a hormone-responsive enzyme (sphingomyelinase) acts on sphingomyelin (precursor metabolite) to form a putative second messenger, ceramide. We hypothesized that ceramide plays a second messenger function in the cellular events producing vasodilatation. Aoric rings from adult male rats were positioned in a muscle bath for measurement of isometric force generation. A concentration-dependent relaxation response to ceramide (10-9M to 10-5 M) was observed in phenylephrine-contracted vessels. At each concentration of ceramide, the dilator response was transient; at 1 μM the duration was approximately 5 minutes. No relaxation was observed in 60 mM KCl-contracted rings. Relaxation to ceramide was partially inhibited (∼50%) by Nω-nitro-L-arginine (10-4 M) and methylene blue (10-5 M) and by mechanical removal of the endothelium (figure). The phosphatase inhibitor, okadaic acid (10 nM) reduced relaxation to the second messenger (1 μM) bv anoroximatelv 50%. These studies define a signaling function of ceramide in vascular smooth muscle relaxation. We conclude that the vasodilator activity of the second messenger is augmented by activating nitric oxide synthase and that its inhibition may be due to stimulation of a ceramidesensitive phosphatase. (Supported by NIH HL-18575).

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

Fingerprint

Ceramides
Second Messenger Systems
Vascular Smooth Muscle
Muscle
Phosphoric Monoester Hydrolases
Sphingomyelin Phosphodiesterase
Okadaic Acid
Muscle Relaxation
Sphingomyelins
Methylene Blue
Phenylephrine
Metabolites
Vasodilator Agents
Baths
Vasodilation
Nitric Oxide Synthase
Transient analysis
Endothelium
Arginine
Rats

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Ceram, a novel second messenger relaxes vascular smooth muscle. / Jin, J. S.; Webb, R Clinton.

In: FASEB Journal, Vol. 10, No. 3, 01.12.1996.

Research output: Contribution to journalArticle

@article{0fa9fe2206a543ddabc9dc51f9e424e1,
title = "Ceram, a novel second messenger relaxes vascular smooth muscle",
abstract = "Recent findings demonstrate a hormone-responsive enzyme (sphingomyelinase) acts on sphingomyelin (precursor metabolite) to form a putative second messenger, ceramide. We hypothesized that ceramide plays a second messenger function in the cellular events producing vasodilatation. Aoric rings from adult male rats were positioned in a muscle bath for measurement of isometric force generation. A concentration-dependent relaxation response to ceramide (10-9M to 10-5 M) was observed in phenylephrine-contracted vessels. At each concentration of ceramide, the dilator response was transient; at 1 μM the duration was approximately 5 minutes. No relaxation was observed in 60 mM KCl-contracted rings. Relaxation to ceramide was partially inhibited (∼50{\%}) by Nω-nitro-L-arginine (10-4 M) and methylene blue (10-5 M) and by mechanical removal of the endothelium (figure). The phosphatase inhibitor, okadaic acid (10 nM) reduced relaxation to the second messenger (1 μM) bv anoroximatelv 50{\%}. These studies define a signaling function of ceramide in vascular smooth muscle relaxation. We conclude that the vasodilator activity of the second messenger is augmented by activating nitric oxide synthase and that its inhibition may be due to stimulation of a ceramidesensitive phosphatase. (Supported by NIH HL-18575).",
author = "Jin, {J. S.} and Webb, {R Clinton}",
year = "1996",
month = "12",
day = "1",
language = "English (US)",
volume = "10",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - Ceram, a novel second messenger relaxes vascular smooth muscle

AU - Jin, J. S.

AU - Webb, R Clinton

PY - 1996/12/1

Y1 - 1996/12/1

N2 - Recent findings demonstrate a hormone-responsive enzyme (sphingomyelinase) acts on sphingomyelin (precursor metabolite) to form a putative second messenger, ceramide. We hypothesized that ceramide plays a second messenger function in the cellular events producing vasodilatation. Aoric rings from adult male rats were positioned in a muscle bath for measurement of isometric force generation. A concentration-dependent relaxation response to ceramide (10-9M to 10-5 M) was observed in phenylephrine-contracted vessels. At each concentration of ceramide, the dilator response was transient; at 1 μM the duration was approximately 5 minutes. No relaxation was observed in 60 mM KCl-contracted rings. Relaxation to ceramide was partially inhibited (∼50%) by Nω-nitro-L-arginine (10-4 M) and methylene blue (10-5 M) and by mechanical removal of the endothelium (figure). The phosphatase inhibitor, okadaic acid (10 nM) reduced relaxation to the second messenger (1 μM) bv anoroximatelv 50%. These studies define a signaling function of ceramide in vascular smooth muscle relaxation. We conclude that the vasodilator activity of the second messenger is augmented by activating nitric oxide synthase and that its inhibition may be due to stimulation of a ceramidesensitive phosphatase. (Supported by NIH HL-18575).

AB - Recent findings demonstrate a hormone-responsive enzyme (sphingomyelinase) acts on sphingomyelin (precursor metabolite) to form a putative second messenger, ceramide. We hypothesized that ceramide plays a second messenger function in the cellular events producing vasodilatation. Aoric rings from adult male rats were positioned in a muscle bath for measurement of isometric force generation. A concentration-dependent relaxation response to ceramide (10-9M to 10-5 M) was observed in phenylephrine-contracted vessels. At each concentration of ceramide, the dilator response was transient; at 1 μM the duration was approximately 5 minutes. No relaxation was observed in 60 mM KCl-contracted rings. Relaxation to ceramide was partially inhibited (∼50%) by Nω-nitro-L-arginine (10-4 M) and methylene blue (10-5 M) and by mechanical removal of the endothelium (figure). The phosphatase inhibitor, okadaic acid (10 nM) reduced relaxation to the second messenger (1 μM) bv anoroximatelv 50%. These studies define a signaling function of ceramide in vascular smooth muscle relaxation. We conclude that the vasodilator activity of the second messenger is augmented by activating nitric oxide synthase and that its inhibition may be due to stimulation of a ceramidesensitive phosphatase. (Supported by NIH HL-18575).

UR - http://www.scopus.com/inward/record.url?scp=33748975567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748975567&partnerID=8YFLogxK

M3 - Article

VL - 10

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -