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Factors involved in the relaxation of female pig urethra evoked by electrical field stimulation

Werkström, Viktoria LU ; Persson, Katarina LU ; Ny, Lars; Bridgewater, Melissa; Brading, Alison F and Andersson, Karl-Erik LU (1995) In British Journal of Pharmacology 116(1). p.1599-1604
Abstract
1 Non-adrenergic, non-cholinergic (NANC) relaxations induced by electrical field stimulation (EFS)were studied in pig isolated urethra. The mechanism for relaxation was characterized by measurement of cyclic nucleotides and by study of involvement of different subsets of voltage-operated calcium channels (VOCCs).

2 EFS evoked frequency-dependent and tetrodotoxin-sensitive relaxations in the presence of propranolol (1 yM), phentolamine (1 pM) and scopolamine (1 pM). At low frequencies (< 12 Hz),

relaxations were rapid, whereas at high (> 12 Hz) frequencies distinct biphasic relaxations were evoked.

The latter consisted of a rapidly developing first phase followed by a more long-lasting second... (More)
1 Non-adrenergic, non-cholinergic (NANC) relaxations induced by electrical field stimulation (EFS)were studied in pig isolated urethra. The mechanism for relaxation was characterized by measurement of cyclic nucleotides and by study of involvement of different subsets of voltage-operated calcium channels (VOCCs).

2 EFS evoked frequency-dependent and tetrodotoxin-sensitive relaxations in the presence of propranolol (1 yM), phentolamine (1 pM) and scopolamine (1 pM). At low frequencies (< 12 Hz),

relaxations were rapid, whereas at high (> 12 Hz) frequencies distinct biphasic relaxations were evoked.

The latter consisted of a rapidly developing first phase followed by a more long-lasting second phase.

3 Treatment with the NO-synthesis inhibitor N0-nitro-L-arginine (L-NOARG; 0.3 mM) inhibited relaxations at low frequencies of stimulation. At high frequencies (> 12 Hz) only the first relaxation phase was affected.

4 Measurement of cyclic nucleotides in preparations subjected to continuous nerve-stimulation, revealed an increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels from 1.3 ± 0.3 to 3.0±0.4 pmol mg'- protein (P<0.01). In the presence of L-NOARG, there was a significant decrease in cyclic GMP content to control. However, there was no increase in cyclic GMP content in response to EFS. Levels of cyclic AMP remained unchanged following EFS.

5 Treatment with the N-type VOCC-inhibitor, wo-conotoxin GVIA (0.1 FM) reduced NO-dependent relaxations, the effect being most pronounced at low frequencies (1-4 Hz) of stimulation. The NOindependent second phase of the relaxation, studied in the presence of L-NOARG (0.3 mM) at 16- 30 Hz, was however markedly reduced or abolished by w-conotoxin GVIA. w-Conotoxin MVIIC (1 pM)or w-agatoxin IVA (30 nM) had no effect on electrically evoked relaxations.

6 These results suggest that NANC-nerve derived urethral relaxation in the pig consists of two apparently independent components. One is mediated by NO and associated with an increase in cyclic GMP content. The other mediator is unknown and produces relaxations not associated with changes in levels of cyclic nucleotides. The release of this mediator seems to involve the N-type VOCC, since the relaxation was markedly reduced or abolished by w-conotoxin GVIA. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
smooth muscle relaxation, nitric oxide, a-conotoxin, NANC neurotransmission, cyclic nucleotides, calcium channels, urethra
in
British Journal of Pharmacology
volume
116
issue
1
pages
1599 - 1604
publisher
The British Pharmacological Society
external identifiers
  • pmid:8564225
  • scopus:0029089944
ISSN
1476-5381
language
English
LU publication?
yes
id
c04cb284-d1a1-4ffb-b9fc-720e49dc2ea2 (old id 1109134)
date added to LUP
2008-07-25 14:11:34
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2017-01-01 07:21:22
@article{c04cb284-d1a1-4ffb-b9fc-720e49dc2ea2,
  abstract     = {1 Non-adrenergic, non-cholinergic (NANC) relaxations induced by electrical field stimulation (EFS)were studied in pig isolated urethra. The mechanism for relaxation was characterized by measurement of cyclic nucleotides and by study of involvement of different subsets of voltage-operated calcium channels (VOCCs). <br/><br>
2 EFS evoked frequency-dependent and tetrodotoxin-sensitive relaxations in the presence of propranolol (1 yM), phentolamine (1 pM) and scopolamine (1 pM). At low frequencies (&lt; 12 Hz),<br/><br>
relaxations were rapid, whereas at high (&gt; 12 Hz) frequencies distinct biphasic relaxations were evoked.<br/><br>
The latter consisted of a rapidly developing first phase followed by a more long-lasting second phase.<br/><br>
3 Treatment with the NO-synthesis inhibitor N0-nitro-L-arginine (L-NOARG; 0.3 mM) inhibited relaxations at low frequencies of stimulation. At high frequencies (&gt; 12 Hz) only the first relaxation phase was affected.<br/><br>
4 Measurement of cyclic nucleotides in preparations subjected to continuous nerve-stimulation, revealed an increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels from 1.3 ± 0.3 to 3.0±0.4 pmol mg'- protein (P&lt;0.01). In the presence of L-NOARG, there was a significant decrease in cyclic GMP content to control. However, there was no increase in cyclic GMP content in response to EFS. Levels of cyclic AMP remained unchanged following EFS.<br/><br>
5 Treatment with the N-type VOCC-inhibitor, wo-conotoxin GVIA (0.1 FM) reduced NO-dependent relaxations, the effect being most pronounced at low frequencies (1-4 Hz) of stimulation. The NOindependent second phase of the relaxation, studied in the presence of L-NOARG (0.3 mM) at 16- 30 Hz, was however markedly reduced or abolished by w-conotoxin GVIA. w-Conotoxin MVIIC (1 pM)or w-agatoxin IVA (30 nM) had no effect on electrically evoked relaxations.<br/><br>
6 These results suggest that NANC-nerve derived urethral relaxation in the pig consists of two apparently independent components. One is mediated by NO and associated with an increase in cyclic GMP content. The other mediator is unknown and produces relaxations not associated with changes in levels of cyclic nucleotides. The release of this mediator seems to involve the N-type VOCC, since the relaxation was markedly reduced or abolished by w-conotoxin GVIA.},
  author       = {Werkström, Viktoria and Persson, Katarina and Ny, Lars and Bridgewater, Melissa and Brading, Alison F and Andersson, Karl-Erik},
  issn         = {1476-5381},
  keyword      = {smooth muscle relaxation,nitric oxide,a-conotoxin,NANC neurotransmission,cyclic nucleotides,calcium
channels,urethra},
  language     = {eng},
  number       = {1},
  pages        = {1599--1604},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Factors involved in the relaxation of female pig urethra evoked by electrical field stimulation},
  volume       = {116},
  year         = {1995},
}