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Carbon monoxide relaxes the female pig urethra as effectively as nitric oxide in the presence of YC-1.

Schroder, Annette; Hedlund, Petter LU and Andersson, Karl-Erik LU (2002) In Journal of Urology 167(4). p.1892-1896
Abstract
PURPOSE: Nitric oxide (NO) and carbon monoxide (CO) have been suggested to relax smooth muscle by activating soluble guanylate cyclase (sGC), binding to the same site of the enzyme. 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) (Cayman Co., Malmö, Sweden) increases the catalytic rate of sGC by binding to an allosteric site. We investigated whether YC-1 can modulate the relaxant responses of isolated urethral smooth muscle to exogenous CO, (NO) and electrical field stimulation. MATERIALS AND METHODS: In spontaneously active and noradrenaline (Sigma-Aldrich Chemie GmbH, Steinheim, Germany) pre-contracted preparations of circular urethral smooth muscle from female pigs relaxant responses were evoked by electrical field stimulation... (More)
PURPOSE: Nitric oxide (NO) and carbon monoxide (CO) have been suggested to relax smooth muscle by activating soluble guanylate cyclase (sGC), binding to the same site of the enzyme. 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) (Cayman Co., Malmö, Sweden) increases the catalytic rate of sGC by binding to an allosteric site. We investigated whether YC-1 can modulate the relaxant responses of isolated urethral smooth muscle to exogenous CO, (NO) and electrical field stimulation. MATERIALS AND METHODS: In spontaneously active and noradrenaline (Sigma-Aldrich Chemie GmbH, Steinheim, Germany) pre-contracted preparations of circular urethral smooth muscle from female pigs relaxant responses were evoked by electrical field stimulation before and after incubation with 10(-5) M. YC-1. The concentration-response curves for CO and NO were investigated in noradrenaline pre-contracted strips before and after incubation with YC-1. The tissue contents of cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic adenosine monophosphate after electrical field stimulation, and the administration of CO or NO was investigated in the absence and presence of YC-1. RESULTS: YC-1 significantly increased the amplitude of the relaxations evoked by electrical field stimulation, CO and NO, and simultaneously caused significant increases in the cGMP content in all preparations. The effect on CO induced relaxant responses was conspicuous. In the presence of YC-1 the potency and maximal relaxant effect of CO were similar to those of NO in the absence of YC-1. CONCLUSIONS: YC-1 enhances cGMP dependent relaxant responses of the female pig urethra in vitro. The finding that the response to CO was greatly increased after sensitizing sGC suggests a potential for CO as a relaxant mediator in urethral smooth muscle. (Less)
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keywords
Urethra : physiology, Swine, Non-U.S. Gov't, Support, Nitric Oxide : pharmacology, Muscle Relaxation : physiology, Muscle Relaxation : drug effects, Indazoles : pharmacology, Female, Enzyme Activators : pharmacology, Electric Stimulation, Animal, Carbon Monoxide : pharmacology
in
Journal of Urology
volume
167
issue
4
pages
1892 - 1896
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000174437000112
  • pmid:11912455
  • scopus:0036129642
ISSN
1527-3792
DOI
10.1016/S0022-5347(05)65256-1
language
English
LU publication?
yes
id
0d2548f8-b312-4666-9f67-fcf532c80928 (old id 107160)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11912455&dopt=Abstract
date added to LUP
2007-07-06 07:50:26
date last changed
2017-01-01 07:06:27
@article{0d2548f8-b312-4666-9f67-fcf532c80928,
  abstract     = {PURPOSE: Nitric oxide (NO) and carbon monoxide (CO) have been suggested to relax smooth muscle by activating soluble guanylate cyclase (sGC), binding to the same site of the enzyme. 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) (Cayman Co., Malmö, Sweden) increases the catalytic rate of sGC by binding to an allosteric site. We investigated whether YC-1 can modulate the relaxant responses of isolated urethral smooth muscle to exogenous CO, (NO) and electrical field stimulation. MATERIALS AND METHODS: In spontaneously active and noradrenaline (Sigma-Aldrich Chemie GmbH, Steinheim, Germany) pre-contracted preparations of circular urethral smooth muscle from female pigs relaxant responses were evoked by electrical field stimulation before and after incubation with 10(-5) M. YC-1. The concentration-response curves for CO and NO were investigated in noradrenaline pre-contracted strips before and after incubation with YC-1. The tissue contents of cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic adenosine monophosphate after electrical field stimulation, and the administration of CO or NO was investigated in the absence and presence of YC-1. RESULTS: YC-1 significantly increased the amplitude of the relaxations evoked by electrical field stimulation, CO and NO, and simultaneously caused significant increases in the cGMP content in all preparations. The effect on CO induced relaxant responses was conspicuous. In the presence of YC-1 the potency and maximal relaxant effect of CO were similar to those of NO in the absence of YC-1. CONCLUSIONS: YC-1 enhances cGMP dependent relaxant responses of the female pig urethra in vitro. The finding that the response to CO was greatly increased after sensitizing sGC suggests a potential for CO as a relaxant mediator in urethral smooth muscle.},
  author       = {Schroder, Annette and Hedlund, Petter and Andersson, Karl-Erik},
  issn         = {1527-3792},
  keyword      = {Urethra : physiology,Swine,Non-U.S. Gov't,Support,Nitric Oxide : pharmacology,Muscle Relaxation : physiology,Muscle Relaxation : drug effects,Indazoles : pharmacology,Female,Enzyme Activators : pharmacology,Electric Stimulation,Animal,Carbon Monoxide : pharmacology},
  language     = {eng},
  number       = {4},
  pages        = {1892--1896},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Carbon monoxide relaxes the female pig urethra as effectively as nitric oxide in the presence of YC-1.},
  url          = {http://dx.doi.org/10.1016/S0022-5347(05)65256-1},
  volume       = {167},
  year         = {2002},
}