Receptor-mediated Signal Transduction and Drug Development: Angiotensin II-mediated Signal Transduction, AT1 Receptor Antagonists and ACE Inhibitors in Congestive Heart Failure.
|
Accession number;00A0193258
|
| Title;Receptor-mediated Signal Transduction and Drug Development: Angiotensin II-mediated Signal Transduction, AT1 Receptor Antagonists and ACE Inhibitors in Congestive Heart Failure. |
| Author;
ENDO MASAO
(Yamagata Univ., Sch. of Med.)
SAKURAI KIYOHARU
(Yamagata Univ., Sch. of Med.)
TOMOIKE HITONOBU
(Yamagata Univ., Sch. of Med.)
|
Journal Title;Pharmacometrics
|
Journal Code:S0617A
|
ISSN:0300-8533
|
|
VOL.58;NO.1;PAGE.1-15(1999)
|
| Figure&Table&Reference;FIG.23 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Various types of receptor are distributed on the surface membrane of myocardial cells, which are activated by neurotransmitters, neuropeptides, autacoids and cytokines to lead to the subsequent functional and metabolic adaptation, and altered gene expression and synthesis of functional proteins of the heart. Among these regulatory mechanisms, angiotensin II(Ang II) plays an extremely important role in induction of cardiac hypertrophy and congestive heart failure(CHF). Therapeutic agents that modulate the Ang II-mediated signal transduction are effective in the treatment of patients with CHF. Ang II receptors belong to a family of seven transmembrane G protein coupled receptors. Ang II receptors exist in cardiac tissue, on cell membranes of various types of cells, including myocardial cells, sympathetic nerve endings, fibroblasts, coronary artery smooth muscle and endothelial cells. Two subtypes of Ang II receptors(AT1, AT2) have been cloned. Cardiovascular regulation is mediated largely by activation of AT1 receptors. Intracellular transduction processes triggered by activation of AT1 receptors involve divergent pathways, such as acceleration of PI hydrolysis through activation of PLC.BETA. by Gq and PLC.GAMMA. by tyrosine phosphorylation, and activation of various enzymes, which lead to (1) immediate alteration of activity of ion channels and ion exchangers, and intracellular alkalinization; and (2) long-term regulation of gene expression and protein synthesis that is responsible for cardiac hypertrophy and vascular and cardiac remodeling. AT2 receptors regulate also various processes in cardiovascular cells, including growth inhibition, proapoptosis, cell differentiation, decrease in cellular matrix in the heart, inhibition of cell proliferation, NO production and decrease in cardiac chronotropic effect.... (author abst.) |
|
|
|
Related Articles;
|
|
