Upregulation of the alpha1-adrenoceptor-induced phosphoinositide and inotropic response in hypothyroid rat heart

• Published in: Molecular and cellular biochemistry Vol. 283; no. 1-2; pp. 93 - 100
• Main Authors: Jalali, Shahrzad, Durston, Melanie, Panagia, Vincenzo, Mesaeli, Nasrin
• Format: Journal Article
• Language: English
• Published: Netherlands 01.02.2006
• Subjects: Animals; Antithyroid Agents - pharmacology; Cell Membrane - drug effects; Cell Membrane - metabolism; Heart - drug effects; Heart - physiology; Hypothyroidism - drug therapy; Hypothyroidism - metabolism; Inositol 1,4,5-Trisphosphate - metabolism; Male; Phosphatidylinositol 4,5-Diphosphate - metabolism; Propylthiouracil - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1 - metabolism; Sarcolemma - drug effects; Sarcolemma - metabolism; Signal Transduction; Stimulation, Chemical; Type C Phospholipases - metabolism; Up-Regulation
• ISSN: 0300-8177; 1573-4919

In this study, we examined changes in the biochemical and inotropic events of the alpha(1)-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 beta- and an increase in alpha(1)-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 microM phenylephrine (in the presence of 10 microM atenolol), the increase of contractile parameters over baseline values was significantly higher in hypo- than euthyroid hearts, while the opposite occurred under beta-stimulation with 0.1 microM 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 alpha(1)-adrenoceptor and its associated phosphoinositide signaling pathway may act as a reserve for catecholamine inotropic response in hypothyroidism, where the beta-adrenoceptors are compromised.