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Full-Text Articles in Medicine and Health Sciences
Loss Of Resistance To Angiotensin Ii-Induced Hypertension In The Jackson Laboratory Recombination-Activating Gene Null Mouse On The C57bl/6j Background, Hong Ji, Amrita V Pai, Crystal A West, Xie Wu, Robert Charles Speth, Kathryn Sandberg
Loss Of Resistance To Angiotensin Ii-Induced Hypertension In The Jackson Laboratory Recombination-Activating Gene Null Mouse On The C57bl/6j Background, Hong Ji, Amrita V Pai, Crystal A West, Xie Wu, Robert Charles Speth, Kathryn Sandberg
Faculty Articles
Resistance to angiotensin II (Ang II)–induced hypertension in T-cell–deficient male mice with a targeted mutation in the recombination-activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1−/−-M), which was reported by 5 independent laboratories including ours before 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure induced by 2 weeks of Ang II infusion at 490 ng/kg per minute was identical between B6.Rag1−/−-M and male wild-type littermates. Moreover, there were no differences in the time course or magnitude increase …
An In Vitro And In Vivo Investigation Of Bivalent Ligands That Display Preferential Binding And Functional Activity For Different Melanocortin Receptor Homodimers, Cody J Lensing, Katie T Freeman, Sathya M Schnell, Danielle N Adank, Robert Charles Speth, Carrie Haskell-Luevano
An In Vitro And In Vivo Investigation Of Bivalent Ligands That Display Preferential Binding And Functional Activity For Different Melanocortin Receptor Homodimers, Cody J Lensing, Katie T Freeman, Sathya M Schnell, Danielle N Adank, Robert Charles Speth, Carrie Haskell-Luevano
Faculty Articles
Pharmacological probes for the melanocortin receptors have been utilized for studying various disease states including cancer, sexual function disorders, Alzheimer's disease, social disorders, cachexia, and obesity. This study focused on the design and synthesis of bivalent ligands to target melanocortin receptor homodimers. Lead ligands increased binding affinity by 14- to 25-fold and increased cAMP signaling potency by 3- to 5-fold compared to their monovalent counterparts. Unexpectedly, different bivalent ligands showed preferences for particular melanocortin receptor subtypes depending on the linker that connected the binding scaffolds, suggesting structural differences between the various dimer subtypes. Homobivalent compound 12 possessed a functional profile …