Hong Weng Pang1, Andrea Linares1, Leena Couling1, Jessica Santollo2,3, Leonardo Ancheta4, Derek Daniels2,5, Robert C Speth6,7. 1. College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, FL, 33328, USA. 2. Behavioral Neuroscience Program, Department of Psychology, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA. 3. Department of Biology, University of Kentucky, Lexington, KY, 40506, USA. 4. Advanced Targeting Systems, 10451 Roselle St. #300, San Diego, CA, 92121, USA. 5. Center for Ingestive Behavior Research, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA. 6. College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, FL, 33328, USA. RS1251@nova.edu. 7. Department of Pharmacology and Physiology, College of Medicine, Georgetown University, Washington, DC, 20057, USA. RS1251@nova.edu.
Abstract
PURPOSE: To study the ability of a novel bovine serum albumin-angiotensin II (BSA-Ang II) conjugate to effect responses of the AT1 angiotensin II receptor subtype mediated by the G-protein-coupled and the beta-arrestin pathways. METHODS: Angiotensin II (Ang II) was conjugated with bovine serum albumin and compared with Ang II for competition binding to AT1 receptors, to stimulate aldosterone release from adrenocortical cells, to promote beta-arrestin binding to AT1 receptors, to promote calcium mobilization, and stimulate drinking of water and saline by rats. RESULTS: The BSA-Ang II conjugate was less potent competing for AT1R binding, but was equally efficacious at stimulating aldosterone release from H295R adrenocortical cells. Both BSA-Ang II and Ang II stimulated calcium mobilization and beta-arrestin binding to AT1 receptors. BSA-Ang II and Ang II stimulated water appetite equivalently but BSA-Ang II stimulated saline appetite more than Ang II. Both BSA-Ang II and Ang II were considerably more potent at causing calcium mobilization than β-arrestin binding. CONCLUSIONS: Addition of a high molecular weight molecule to Ang II reduced its AT1 receptor binding affinity, but did not significantly alter stimulation of aldosterone release or water consumption. The BSA-Ang II conjugate caused a greater saline appetite than Ang II suggesting that it may be a more efficacious agonist of this beta-arrestin-mediated response than Ang II. The higher potency calcium signaling response suggests that the G-protein-coupled responses predominate at physiological concentrations of Ang II, while the beta-arrestin response requires pathophysiological or pharmacological concentrations of Ang II to occur.
PURPOSE: To study the ability of a novel bovineserum albumin-angiotensin II (BSA-Ang II) conjugate to effect responses of the AT1angiotensin II receptor subtype mediated by the G-protein-coupled and the beta-arrestin pathways. METHODS:Angiotensin II (Ang II) was conjugated with bovineserum albumin and compared with Ang II for competition binding to AT1 receptors, to stimulate aldosterone release from adrenocortical cells, to promote beta-arrestin binding to AT1 receptors, to promote calcium mobilization, and stimulate drinking of water and saline by rats. RESULTS: The BSA-Ang II conjugate was less potent competing for AT1R binding, but was equally efficacious at stimulating aldosterone release from H295Radrenocortical cells. Both BSA-Ang II and Ang II stimulated calcium mobilization and beta-arrestin binding to AT1 receptors. BSA-Ang II and Ang II stimulated water appetite equivalently but BSA-Ang II stimulated saline appetite more than Ang II. Both BSA-Ang II and Ang II were considerably more potent at causing calcium mobilization than β-arrestin binding. CONCLUSIONS: Addition of a high molecular weight molecule to Ang II reduced its AT1 receptor binding affinity, but did not significantly alter stimulation of aldosterone release or water consumption. The BSA-Ang II conjugate caused a greater saline appetite than Ang II suggesting that it may be a more efficacious agonist of this beta-arrestin-mediated response than Ang II. The higher potency calcium signaling response suggests that the G-protein-coupled responses predominate at physiological concentrations of Ang II, while the beta-arrestin response requires pathophysiological or pharmacological concentrations of Ang II to occur.
Authors: G Mariani; S Ito; R C Nayak; J Baranowska-Kortylewicz; C N Venkateshan; A D Van den Abbeele; G S Eisenbarth; S J Adelstein; A I Kassis Journal: J Nucl Biol Med Date: 1991 Apr-Jun
Authors: H Rasmussen; C M Isales; R Calle; D Throckmorton; M Anderson; J Gasalla-Herraiz; R McCarthy Journal: Endocr Rev Date: 1995-10 Impact factor: 19.871