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 - 1 Feb 2006

    Fingerprint

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this