An antagonistic effect of esmolol on beta-3 adrenoceptor in brown adipose tissue in rats

Esmolol is used in clinical practice as a beta-1 adrenergic antagonist in Europe and North America, but it is still under investigation in Japan. It has a high specificity for beta-1 adrenoceptors relative to the beta-2 subtype. When the antagonizing effect to isoproterenol-induced increase in heart rate (beta-1) or bronchodilation (beta2) is calculated, the ratio of esmolol is reported to be 42.7, which is higher than that of propranolol (0.85) [1]. Based on its high specificity for beta-1 adrenoceptors, esmolol can be used for the treatment of tachycardia in patients with bronchial asthma. Another adrenoceptor subtype, the beta-3 receptor, was found, and its molecular structure was reported by Emorine et al. [2] in 1989. Beta-3 adrenoceptors play roles in thermogenesis, lipolysis, anti-obesity function, and anti-diabetic function, and their genetic variation has been correlated with hereditary obesity and diabetogenesis [3]. Furthermore, their functions in the cardiovascular system have recently been studied [4]. Although the affinities and effects of various drugs affecting beta-adrenoceptors on the beta-3 subtype have been investigated, the effect of esmolol has not been reported, to our knowledge. Beta3 adrenoceptors are distributed in adipose tissues with a high density, and beta-3 adrenergic agonists increase temperature to a greater extent in the interscapular brown adipose tissue than in the rectum in rats [5,6]. In the present study, we investigated the effect of esmolol on the beta-3 adrenoceptors by studying the temperature difference between the interscapular brown adipose tissue and the rectum in rats. The study was approved by our Institutional Animal Care Committee. Forty-five Wistar rats, weighing 200‐300 g, were used. The rats were anesthetized with pentobarbital, 50 mg·kg 1 i.p. A polyethylene catheter (0.9-mm-diameter) was placed in the femoral vein. Thermistor probes were inserted into the interscapular