Molecular cloning and expression of the rat beta 3-adrenergic receptor

Rat adipose tissues contain atypical beta receptors that display certain pharmacological sensitivities that are similar to those found in the recently cloned human beta 3 receptor. However, there are also certain pharmacological differences between the human atypical beta 3 receptor and atypical receptors in rodent adipose tissues, which could indicate strong species differences, the existence of multiple atypical receptor subtypes, or both. To help decide among these possibilities, a rat beta 3 receptor clone was obtained and expressed in Chinese hamster ovary cells. The predicted primary structures of the rat and human receptors are greater than 90% similar. Despite this similarity, the pharmacological properties of the rat receptor differed from those reported for the human receptor but were similar to the properties exhibited by atypical receptors in rat adipose tissue. Specifically, the rat beta 3 receptor had a high affinity for BRL 37344 and a relatively low affinity for norepinephrine and was partially activated by the beta 1 and beta 2 receptor antagonist CGP 12177. Northern blot analysis and nuclease protection assays of RNA from rat tissues indicate that the beta 3 receptor is abundantly expressed only in adipose tissues.