Effect of YM471, an orally active non-peptide arginine vasopressin receptor antagonist, on human vascular smooth muscle cells
| Autor: | Atsuo Tahara, Koh-ichi Wada, Akihiro Tanaka, Nobuaki Taniguchi, Noe Ishii, Yuichi Tomura, Toshiyuki Kusayama, Junko Tsukada, Wataru Uchida, Takeyuki Yatsu |
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| Rok vydání: | 2002 |
| Předmět: |
Receptors
Vasopressin endocrine system medicine.medical_specialty Vasopressin Vascular smooth muscle Arginine Physiology medicine.drug_class Biology Muscle Smooth Vascular Piperidines Internal medicine Internal Medicine medicine Humans Myocyte Kinase activity Receptor Aorta Cells Cultured Vasopressin receptor Hyperplasia Azepines Hypertrophy Receptor antagonist Arginine Vasopressin Enzyme Activation Endocrinology Mitogen-Activated Protein Kinases Cardiology and Cardiovascular Medicine Antidiuretic Hormone Receptor Antagonists hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Hypertension. 20:1807-1814 |
| ISSN: | 0263-6352 |
| DOI: | 10.1097/00004872-200209000-00026 |
| Popis: | Objective To investigate the effects of YM471, a non-peptide arginine vasopressin (AVP) VIA and V 2 receptor antagonist, on the AVP-induced growth responses in human vascular smooth muscle cells (VSMCs). Methods Binding of YM471 to VIA receptors on VSMCs was measured using [ 3 H]AVP. Intracellular free Ca 2+ concentration was measured by fura 2 fluorescence. Mitogen-activated protein (MAP) kinase activity was determined using the p42/p44 MAP kinase specific peptide and [γ- 32 P]ATP as substrates. The effect of AVP on hyperplasia and hypertrophy of VSMCs was determined by cell number and protein content measurements. Results YM471 potently and concentration-dependently inhibited the specific binding of [ 3 H]AVP to VIA receptors on VSMCs, exhibiting an inhibition constant (K i ) of 0.35 nmol/l. YM471 inhibited the AVP-induced increase in intracellular free Ca 2+ concentration with an 50% inhibition concentration (IC 50 ) of 2.01 nmol/l and inhibited the activation of MAP kinase with an IC 50 of 6.11 nmol/l. In addition, AVP concentration-dependently induced hyperplasia and hypertrophy in VSMCs, but YM471 prevented these AVP-induced growth effects, exhibiting IC 50 values of 2.31 and 0.23 nmol/l, respectively. Conclusions These results indicate that YM471 has high affinity for VIA receptors on, and potently inhibits AVP-induced physiologic responses of, human VSMCs. |
| Databáze: | OpenAIRE |
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