[PDF][PDF] Molecular cloning and expression of the rat beta 3-adrenergic receptor.

JG Granneman, KN Lahners, A Chaudhry - Molecular pharmacology, 1991 - Citeseer
JG Granneman, KN Lahners, A Chaudhry
Molecular pharmacology, 1991Citeseer
Rat adipose tissues contain atypical i3 receptors that display certain pharmacological
sensitivities that are similar to those found in the recently cloned human I3 receptor.
However, there are also certain pharmacological differences between the human atypical/33
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 f33 receptor clone was obtained and expressed in …
Summary
Rat adipose tissues contain atypical i3 receptors that display certain pharmacological sensitivities that are similar to those found in the recently cloned human I3 receptor. However, there are also certain pharmacological differences between the human atypical/33 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 f33 receptor clone was obtained and expressed in Chinese hamster ovary cells. The predicted primary structures of the rat and human receptors are
> 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 receptor had a high affinity for BRL 37344 and a relatively low affinity for norepinephrine and was partially activated by the fl and/32 receptor antagonist CGP 12177. Northern blot analysis and nuclease protection assays of RNA from rat tissues indicate that the/33 receptor is abundantly expressed only in adipose tissues.
The nature of the fi adrenergic receptor subtypes in adipose tissue has been controversial. In addition to the well characterized 3,-and fl2-adrenergic receptors, rodent BAT and white adipose tissue contain atypical receptors that display pharmacological properties that are similar to those reported for the human f33 receptor(1-3). For example, both the human/33 receptor and atypical receptors in rat BAT are stimulated by the atypical agonist BRL 37344, and this activity is poorly antagonized by standard/3 receptor antagonists(1, 3-5). However, the atypical receptors controlling adenylyl cyclase activity in rat adipose tissue show several differences in pharmacology from that reported for the human/3 receptor(4, 6, 7). These data indicate that there may be strong species differences with respect to the pharmacology of the/3 receptor, that there may be multiple atypical receptor subtypes, or both. In order to help differentiate among these possibilities, we have cloned a rat homolog of the receptor and have characterized its pharmacological properties in CHO cells. In addition, we have examined the expression of the fl receptor gene in various rat tissues.
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