Upregulation of the α1-adrenoceptor-induced phosphoinositide and inotropic response in hypothyroid rat heart

Shahrzad Jalali, Melanie Durston, Vincenzo Panagia, Nasrin Mesaeli

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In this study, we examined changes in the biochemical and inotropic events of the α1-adrenoceptor signaling pathway in hypothyroid rat hearts. Hypothyroidism was induced by treating experimental animals with 0.05% 6-n-propyl-2-thiouracil (PTU) in drinking water for 7 weeks. A significant decrease of β- and an increase in α1-adrenoceptor density as well as an increase in the basal activity of the phosphoinositide (4,5) bisphosphate hydrolyzing phospholipase C was observed in sarcolemmal membranes purified from hypothyroid hearts as compared to age-matched euthyroid controls. Following stimulation with 10 μM phenylephrine (in the presence of 10 μM atenolol), the increase of contractile parameters over baseline values was significantly higher in hypo- than euthyroid hearts, while the opposite occurred under β-stimulation with 0.1 μM isoproterenol. Interestingly, the increase in phenylephrine-mediated positive inotropy was accompanied by a significant increase in the sarcolemmal phospholipase C activity and in the inositol 1,4,5-trisphosphate content in hypothyroid as compared to euthyroid controls. Our results suggest that cardiac α1 -adrenoceptor and its associated phosphoinositide signaling pathway may act as a reserve for catecholamine inotropic response in hypothyroidism, where the β-adrenoceptors are compromised.

Original languageEnglish
Pages (from-to)93-100
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume283
Issue number1-2
DOIs
Publication statusPublished - Feb 2006
Externally publishedYes

Fingerprint

Phosphatidylinositols
Adrenergic Receptors
Rats
Up-Regulation
Type C Phospholipases
Phenylephrine
Hypothyroidism
Thiouracil
Propylthiouracil
Inositol 1,4,5-Trisphosphate
Atenolol
Isoproterenol
Drinking Water
Catecholamines
Animals
Membranes

Keywords

  • α-adrenoceptor
  • Heart
  • Hyperthyroidism
  • Hypothyroidism
  • Phosphoinositides
  • Phospholipase C
  • Positive inotropy
  • Sarcolemma

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Upregulation of the α1-adrenoceptor-induced phosphoinositide and inotropic response in hypothyroid rat heart. / Jalali, Shahrzad; Durston, Melanie; Panagia, Vincenzo; Mesaeli, Nasrin.

In: Molecular and Cellular Biochemistry, Vol. 283, No. 1-2, 02.2006, p. 93-100.

Research output: Contribution to journalArticle

@article{43e3089773b6410281b37f45f2452798,
title = "Upregulation of the α1-adrenoceptor-induced phosphoinositide and inotropic response in hypothyroid rat heart",
abstract = "In this study, we examined changes in the biochemical and inotropic events of the α1-adrenoceptor signaling pathway in hypothyroid rat hearts. Hypothyroidism was induced by treating experimental animals with 0.05{\%} 6-n-propyl-2-thiouracil (PTU) in drinking water for 7 weeks. A significant decrease of β- and an increase in α1-adrenoceptor density as well as an increase in the basal activity of the phosphoinositide (4,5) bisphosphate hydrolyzing phospholipase C was observed in sarcolemmal membranes purified from hypothyroid hearts as compared to age-matched euthyroid controls. Following stimulation with 10 μM phenylephrine (in the presence of 10 μM atenolol), the increase of contractile parameters over baseline values was significantly higher in hypo- than euthyroid hearts, while the opposite occurred under β-stimulation with 0.1 μM isoproterenol. Interestingly, the increase in phenylephrine-mediated positive inotropy was accompanied by a significant increase in the sarcolemmal phospholipase C activity and in the inositol 1,4,5-trisphosphate content in hypothyroid as compared to euthyroid controls. Our results suggest that cardiac α1 -adrenoceptor and its associated phosphoinositide signaling pathway may act as a reserve for catecholamine inotropic response in hypothyroidism, where the β-adrenoceptors are compromised.",
keywords = "α-adrenoceptor, Heart, Hyperthyroidism, Hypothyroidism, Phosphoinositides, Phospholipase C, Positive inotropy, Sarcolemma",
author = "Shahrzad Jalali and Melanie Durston and Vincenzo Panagia and Nasrin Mesaeli",
year = "2006",
month = "2",
doi = "10.1007/s11010-006-2348-9",
language = "English",
volume = "283",
pages = "93--100",
journal = "Molecular and Cellular Biochemistry",
issn = "0300-8177",
publisher = "Springer Netherlands",
number = "1-2",

}

TY - JOUR

T1 - Upregulation of the α1-adrenoceptor-induced phosphoinositide and inotropic response in hypothyroid rat heart

AU - Jalali, Shahrzad

AU - Durston, Melanie

AU - Panagia, Vincenzo

AU - Mesaeli, Nasrin

PY - 2006/2

Y1 - 2006/2

N2 - In this study, we examined changes in the biochemical and inotropic events of the α1-adrenoceptor signaling pathway in hypothyroid rat hearts. Hypothyroidism was induced by treating experimental animals with 0.05% 6-n-propyl-2-thiouracil (PTU) in drinking water for 7 weeks. A significant decrease of β- and an increase in α1-adrenoceptor density as well as an increase in the basal activity of the phosphoinositide (4,5) bisphosphate hydrolyzing phospholipase C was observed in sarcolemmal membranes purified from hypothyroid hearts as compared to age-matched euthyroid controls. Following stimulation with 10 μM phenylephrine (in the presence of 10 μM atenolol), the increase of contractile parameters over baseline values was significantly higher in hypo- than euthyroid hearts, while the opposite occurred under β-stimulation with 0.1 μM isoproterenol. Interestingly, the increase in phenylephrine-mediated positive inotropy was accompanied by a significant increase in the sarcolemmal phospholipase C activity and in the inositol 1,4,5-trisphosphate content in hypothyroid as compared to euthyroid controls. Our results suggest that cardiac α1 -adrenoceptor and its associated phosphoinositide signaling pathway may act as a reserve for catecholamine inotropic response in hypothyroidism, where the β-adrenoceptors are compromised.

AB - In this study, we examined changes in the biochemical and inotropic events of the α1-adrenoceptor signaling pathway in hypothyroid rat hearts. Hypothyroidism was induced by treating experimental animals with 0.05% 6-n-propyl-2-thiouracil (PTU) in drinking water for 7 weeks. A significant decrease of β- and an increase in α1-adrenoceptor density as well as an increase in the basal activity of the phosphoinositide (4,5) bisphosphate hydrolyzing phospholipase C was observed in sarcolemmal membranes purified from hypothyroid hearts as compared to age-matched euthyroid controls. Following stimulation with 10 μM phenylephrine (in the presence of 10 μM atenolol), the increase of contractile parameters over baseline values was significantly higher in hypo- than euthyroid hearts, while the opposite occurred under β-stimulation with 0.1 μM isoproterenol. Interestingly, the increase in phenylephrine-mediated positive inotropy was accompanied by a significant increase in the sarcolemmal phospholipase C activity and in the inositol 1,4,5-trisphosphate content in hypothyroid as compared to euthyroid controls. Our results suggest that cardiac α1 -adrenoceptor and its associated phosphoinositide signaling pathway may act as a reserve for catecholamine inotropic response in hypothyroidism, where the β-adrenoceptors are compromised.

KW - α-adrenoceptor

KW - Heart

KW - Hyperthyroidism

KW - Hypothyroidism

KW - Phosphoinositides

KW - Phospholipase C

KW - Positive inotropy

KW - Sarcolemma

UR - http://www.scopus.com/inward/record.url?scp=33645768790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645768790&partnerID=8YFLogxK

U2 - 10.1007/s11010-006-2348-9

DO - 10.1007/s11010-006-2348-9

M3 - Article

C2 - 16444590

AN - SCOPUS:33645768790

VL - 283

SP - 93

EP - 100

JO - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

SN - 0300-8177

IS - 1-2

ER -