Targeted disruption of the beta2 adrenergic receptor gene.
نویسندگان
چکیده
beta-Adrenergic receptors (beta-ARs) are members of the superfamily of G-protein-coupled receptors that mediate the effects of catecholamines in the sympathetic nervous system. Three distinct beta-AR subtypes have been identified (beta1-AR, beta2-AR, and beta3-AR). In order to define further the role of the different beta-AR subtypes, we have used gene targeting to inactivate selectively the beta2-AR gene in mice. Based on intercrosses of heterozygous knockout (beta2-AR +/-) mice, there is no prenatal lethality associated with this mutation. Adult knockout mice (beta2-AR -/-) appear grossly normal and are fertile. Their resting heart rate and blood pressure are normal, and they have a normal chronotropic response to the beta-AR agonist isoproterenol. The hypotensive response to isoproterenol, however, is significantly blunted compared with wild type mice. Despite this defect in vasodilation, beta2-AR -/- mice can still exercise normally and actually have a greater total exercise capacity than wild type mice. At comparable workloads, beta2-AR -/- mice had a lower respiratory exchange ratio than wild type mice suggesting a difference in energy metabolism. beta2-AR -/- mice become hypertensive during exercise and exhibit a greater hypertensive response to epinephrine compared with wild type mice. In summary, the primary physiologic consequences of the beta2-AR gene disruption are observed only during the stress of exercise and are the result of alterations in both vascular tone and energy metabolism.
منابع مشابه
Effects of three beta adrenergic receptor agonists on growth performance, blood biochemical parameters, fatty acids composition and carnitine palmitoyltransferase I gene expression of rainbow trout, Oncorhynchus mykiss
Different beta 1 and 2 adrenergic receptors agonists might have various biological and physiological effects on fish species. An experiment was designed to study the effects of feeding ractopamine, terbutaline and metaproterenol; as beta1, beta2 and less selective beta2 adrenergic receptor agonists, respectively; on body weight gain, feed conversion rate, concentration of biochemical parameters...
متن کاملEffects of three beta adrenergic receptor agonists on growth performance, blood biochemical parameters, fatty acids composition and carnitine palmitoyltransferase I gene expression of rainbow trout Oncorhynchus mykiss
Different beta 1 and 2 adrenergic receptor agonists may be various biological and physiological effects on fish species. An experiment was designed to study the effects of feeding ractopamine, terbutaline and metaproterenol; as beta1, beta2 and less selective beta 2 adrenergic receptor agonists, respectively; on body weight gain, feed conversion ratio, concentration of biochemical parameters in...
متن کاملInvestigation of adrenoceptor genes (β2 & β3) in women with polycystic ovary syndrome
Background: Genetic polymorphism is responsible for variations and individual differences. Polymorphism is a major factor of complex diseases with unknown etiology and cancer. Inconsistency in the symptoms of polycystic ovary syndrome (monthly disorder, hirsutism, obesity, diabetes, infertility) is one of the major pathological complications of this syndrome. The present study was conducted to ...
متن کاملPTH regulates β2-adrenergic receptor expression in osteoblast-like MC3T3-E1 cells.
As the aged population is soaring, prevalence of osteoporosis is increasing. However, the molecular basis underlying the regulation of bone mass is still incompletely understood. Sympathetic tone acts via beta2 adrenergic receptors in bone and regulates the mass of bone which is the target organ of parathyroid hormone (PTH). However, whether beta2 adrenergic receptor is regulated by PTH in bone...
متن کاملContribution of potassium channels, beta2-adrenergic and histamine H1 receptors in the relaxant effect of baicalein on rat tracheal smooth muscle
Objective(s): Baicalein, a compound extracted from a variety of herbs, showed various pharmacological effects. This study evaluated the relaxant effects of baicalein and its underlying molecular mechanisms of action on rat’s isolated tracheal smooth muscle.Materials and Methods: Tracheal smooth muscle were contracted by 10 μM methacholin...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 274 24 شماره
صفحات -
تاریخ انتشار 1999