MOLECULAR-CLONING AND EXPRESSION OF THE RAT BETA-3-ADRENERGIC RECEPTOR

Rat adipose tissues contain atypical beta-receptors that display certa in pharmacological sensitivities that are similar to those found in th e recently cloned human beta-3 receptor. However, there are also certa in pharmacological differences between the human atypical beta-3 recep tor and atypical receptors in rodent adipose tissues, which could indi cate strong species differences, the existence of multiple atypical re ceptor subtypes, or both. To help decide among these possibilities, a rat beta-3 receptor clone was obtained and expressed in Chinese hamste r ovary cells. The predicted primary structures of the rat and human r eceptors are > 90% similar. Despite this similarity, the pharmacologic al properties of the rat receptor differed from those reported for the human receptor but were similar to the properties exhibited by atypic al receptors in rat adipose tissue. Specifically, the rat beta-3 recep tor had a high affinity for BRL 37344 and a relatively low affinity fo r norepinephrine and was partially activated by the beta-1 and beta-2 receptor antagonist CGP 12177. Northern blot analysis and nuclease pro tection assays of RNA from rat tissues indicate that the beta-3 recept or is abundantly expressed only in adipose tissues.