0000000000004132
AUTHOR
Betül R Erdogan
Building Robustness into Translational Research
AbstractNonclinical studies form the basis for the decision whether to take a therapeutic candidate into the clinic. These studies need to exhibit translational robustness for both ethical and economic reasons. Key findings confirmed in multiple species have a greater chance to also occur in humans. Given the heterogeneity of patient populations, preclinical studies or at least programs comprising multiple studies need to reflect such heterogeneity, e.g., regarding strains, sex, age, and comorbidities of experimental animals. However, introducing such heterogeneity requires larger studies/programs to maintain statistical power in the face of greater variability. In addition to classic sourc…
Validation of Fenoterol to Study β<sub>2</sub>-Adrenoceptor Function in the Rat Urinary Bladder
Fenoterol is a β<sub>2</sub>-adrenoceptor (AR)-selective agonist that is commonly used to investigate relaxation responses mediated by β<sub>2</sub>-AR in smooth muscle preparations. Some data have questioned this because fenoterol had low potency in the rat urinary bladder when a muscarinic agonist was used as a pre-contraction agent and because some investigators proposed that fenoterol may act in part via β<sub>3</sub>-AR. We designed the present study to investigate whether fenoterol is a proper pharmacological tool to study β<sub>2</sub>-AR-mediated relaxation responses in the rat urinary bladder. Firstly, we have compared the effect of p…
Expression and Signaling of β-Adrenoceptor Subtypes in the Diabetic Heart.
Diabetes is a chronic, endocrine disorder that effects millions of people worldwide. Cardiovascular complications are the major cause of diabetes-related morbidity and mortality. Cardiac β1- and β2-adrenoceptor (AR) stimulation mediates positive inotropy and chronotropy, whereas β3-AR mediates negative inotropic effect. Changes in β-AR responsiveness are thought to be an important factor that contributes to the diabetic cardiac dysfunction. Diabetes related changes in β-AR expression, signaling, and β-AR mediated cardiac function have been studied by several investigators for many years. In the present review, we have screened PubMed database to obtain relevant articles on this topic. Our s…