Tocolytic therapy with fenoterol induces selective down-regulation
of beta-adrenergic receptors in human myometrium
S. Engelhardt, W. Zieger, J. Kassubek, M. Michel, M. Lohse, and O. Brodde. J Clin Endocrinol Metab, 82 (4):
1235-42(April 1997)Engelhardt, S Zieger, W Kassubek, J Michel, M C Lohse, M J Brodde,
O E Research Support, Non-U.S. Gov't United states The Journal of
clinical endocrinology and metabolism J Clin Endocrinol Metab. 1997
Apr;82(4):1235-42..
Abstract
Tocolytic therapy with beta-adrenergic receptor agonists is a standard
regimen to prevent preterm birth. Agonists exposure of beta-adrenergic
receptors causes receptor desensitization in other organs, and this
may limit the therapeutic value of beta-adrenergic receptor agonists.
To study the effects of prolonged beta-adrenergic agonist treatment
in human myometrium, we obtained biopsies during Caesarean section
of 14 pregnant patients who had received fenoterol for at least 5
days and 14 untreated pregnant controls. The densities of total beta-adrenergic
receptors, which are mainly of the beta 2-subtype as assessed by
125Iiodo-cyanopindolol binding in crude membrane fractions, were
more than 50% smaller in women receiving fenoterol, whereas alpha
2-adrenergic receptor densities were similar. Gs and Gi G-protein
alpha-subunit densities were unaltered as assessed by Western blotting
and pertussis toxin-catalyzed 32PADP-ribosylation. beta-Adrenergic
receptor kinase (beta ARK) activity, as determined using bovine rhodopsin
as the substrate, was the same in the two groups. Adenylyl cyclase
activities in the presence of guanine nucleotides, NaF, forskolin,
or Mn+2 were also not altered by fenoterol treatment. The messenger
RNA (mRNA) concentrations of beta 2-adrenergic receptors, beta ARK-I
and glyceraldehyde-3-phosphate dehydrogenase (as a reference), as
determined by quantitative PCR, were unaffected by fenoterol treatment.
We conclude that tocolysis with fenoterol results in a selective
down-regulation of myometrial beta-adrenergic receptors, which is
not associated with a reduction in the respective mRNA concentrations
or alterations of alpha 2-adrenergic receptors, Gs and Gi alpha-subunits,
or beta ARK activity or mRNA.
Engelhardt, S Zieger, W Kassubek, J Michel, M C Lohse, M J Brodde,
O E Research Support, Non-U.S. Gov't United states The Journal of
clinical endocrinology and metabolism J Clin Endocrinol Metab. 1997
Apr;82(4):1235-42.
%0 Journal Article
%1 Engelhardt1997
%A Engelhardt, S.
%A Zieger, W.
%A Kassubek, J.
%A Michel, M. C.
%A Lohse, M. J.
%A Brodde, O. E.
%D 1997
%J J Clin Endocrinol Metab
%K *Down-Regulation AMP-Dependent Adult Agents/*pharmacology Cyclic Female Fenoterol/*pharmacology GTP-Binding Humans Kinases Kinases/metabolism Messenger/metabolism Myometrium/*drug Pregnancy Protein Proteins/metabolism RNA, Receptor Tocolytic beta-Adrenergic beta/*drug effects/*metabolism effects/genetics/metabolism Adrenergic
%N 4
%P 1235-42
%T Tocolytic therapy with fenoterol induces selective down-regulation
of beta-adrenergic receptors in human myometrium
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9100601
%V 82
%X Tocolytic therapy with beta-adrenergic receptor agonists is a standard
regimen to prevent preterm birth. Agonists exposure of beta-adrenergic
receptors causes receptor desensitization in other organs, and this
may limit the therapeutic value of beta-adrenergic receptor agonists.
To study the effects of prolonged beta-adrenergic agonist treatment
in human myometrium, we obtained biopsies during Caesarean section
of 14 pregnant patients who had received fenoterol for at least 5
days and 14 untreated pregnant controls. The densities of total beta-adrenergic
receptors, which are mainly of the beta 2-subtype as assessed by
125Iiodo-cyanopindolol binding in crude membrane fractions, were
more than 50% smaller in women receiving fenoterol, whereas alpha
2-adrenergic receptor densities were similar. Gs and Gi G-protein
alpha-subunit densities were unaltered as assessed by Western blotting
and pertussis toxin-catalyzed 32PADP-ribosylation. beta-Adrenergic
receptor kinase (beta ARK) activity, as determined using bovine rhodopsin
as the substrate, was the same in the two groups. Adenylyl cyclase
activities in the presence of guanine nucleotides, NaF, forskolin,
or Mn+2 were also not altered by fenoterol treatment. The messenger
RNA (mRNA) concentrations of beta 2-adrenergic receptors, beta ARK-I
and glyceraldehyde-3-phosphate dehydrogenase (as a reference), as
determined by quantitative PCR, were unaffected by fenoterol treatment.
We conclude that tocolysis with fenoterol results in a selective
down-regulation of myometrial beta-adrenergic receptors, which is
not associated with a reduction in the respective mRNA concentrations
or alterations of alpha 2-adrenergic receptors, Gs and Gi alpha-subunits,
or beta ARK activity or mRNA.
@article{Engelhardt1997,
abstract = {Tocolytic therapy with beta-adrenergic receptor agonists is a standard
regimen to prevent preterm birth. Agonists exposure of beta-adrenergic
receptors causes receptor desensitization in other organs, and this
may limit the therapeutic value of beta-adrenergic receptor agonists.
To study the effects of prolonged beta-adrenergic agonist treatment
in human myometrium, we obtained biopsies during Caesarean section
of 14 pregnant patients who had received fenoterol for at least 5
days and 14 untreated pregnant controls. The densities of total beta-adrenergic
receptors, which are mainly of the beta 2-subtype as assessed by
[125I]iodo-cyanopindolol binding in crude membrane fractions, were
more than 50% smaller in women receiving fenoterol, whereas alpha
2-adrenergic receptor densities were similar. Gs and Gi G-protein
alpha-subunit densities were unaltered as assessed by Western blotting
and pertussis toxin-catalyzed [32P]ADP-ribosylation. beta-Adrenergic
receptor kinase (beta ARK) activity, as determined using bovine rhodopsin
as the substrate, was the same in the two groups. Adenylyl cyclase
activities in the presence of guanine nucleotides, NaF, forskolin,
or Mn+2 were also not altered by fenoterol treatment. The messenger
RNA (mRNA) concentrations of beta 2-adrenergic receptors, beta ARK-I
and glyceraldehyde-3-phosphate dehydrogenase (as a reference), as
determined by quantitative PCR, were unaffected by fenoterol treatment.
We conclude that tocolysis with fenoterol results in a selective
down-regulation of myometrial beta-adrenergic receptors, which is
not associated with a reduction in the respective mRNA concentrations
or alterations of alpha 2-adrenergic receptors, Gs and Gi alpha-subunits,
or beta ARK activity or mRNA.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Engelhardt, S. and Zieger, W. and Kassubek, J. and Michel, M. C. and Lohse, M. J. and Brodde, O. E.},
biburl = {https://www.bibsonomy.org/bibtex/266ec5e100f6718db192c64bb4f2661ea/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {3e27f085b08f097786ef048491134dc7},
intrahash = {66ec5e100f6718db192c64bb4f2661ea},
issn = {0021-972X (Print) 0021-972X (Linking)},
journal = {J Clin Endocrinol Metab},
keywords = {*Down-Regulation AMP-Dependent Adult Agents/*pharmacology Cyclic Female Fenoterol/*pharmacology GTP-Binding Humans Kinases Kinases/metabolism Messenger/metabolism Myometrium/*drug Pregnancy Protein Proteins/metabolism RNA, Receptor Tocolytic beta-Adrenergic beta/*drug effects/*metabolism effects/genetics/metabolism Adrenergic},
month = Apr,
note = {Engelhardt, S Zieger, W Kassubek, J Michel, M C Lohse, M J Brodde,
O E Research Support, Non-U.S. Gov't United states The Journal of
clinical endocrinology and metabolism J Clin Endocrinol Metab. 1997
Apr;82(4):1235-42.},
number = 4,
pages = {1235-42},
shorttitle = {Tocolytic therapy with fenoterol induces selective down-regulation
of beta-adrenergic receptors in human myometrium},
timestamp = {2010-12-14T18:22:39.000+0100},
title = {Tocolytic therapy with fenoterol induces selective down-regulation
of beta-adrenergic receptors in human myometrium},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9100601},
volume = 82,
year = 1997
}