Receptores Beta 3

Romanian Journal of Morphology and Embryology 2009, 50(2):169–179

REVIEW
Beta 3 adrenergic receptors: molecular,
histological, functional and pharmacological
approaches
OANA ANDREIA COMAN1), H. PĂUNESCU1), ISABEL GHIŢĂ1),
L. COMAN2), ANCA BĂDĂRĂRU2), I. FULGA1)
1)

Department of Pharmacology and Pharmacotherapy
2)
Department of Physiology

Faculty of Medicine,
“Carol Davila” University ofMedicine and Pharmacy, Bucharest

Abstract

Different classes of receptors mediate norepinephrine and epinephrine effects, one of the most recently discovered being the beta 3
adrenergic ones. The paper has proposed itself to present the history of the discovery of beta 3 adrenergic receptors, different techniques
for their identification, their structure, localization, genetic data and also themechanism of regulation of their functions. It also contains an
exhaustive approach regarding the histological localization and functions of beta 3 adrenergic receptors in different apparatus and
systems, making evident their effect on glucidic, lipidic and energetic metabolism. The substances that influence beta 3 adrenergic
receptors activities, especially the agonists, have been studied regardingtheir practical applications in the treatment of diabetes mellitus
and of the disturbances of lipid metabolism.
Keywords: beta 3 adrenergic receptors, discovery, histology, molecular biology, physiology, pharmacology.

Discovery of beta 3 adrenergic receptors
A class of membrane proteins called adrenergic
receptors mediates the multiple metabolic and
neuroendocrine
effects
of
epinephrine
andnorepinephrine. These receptors are coupled with G
proteins, which in turn interact with intracellular
effectors (secondary messengers) such as adenylyl
cyclase or phospholipase C.
These receptors were initially divided in two types:
alpha and beta [1]. Nevertheless, in some tissues as the
white and brown fat tissue and the digestive tract some
effects mediated by beta-receptors such as lipolysis,
oxygenconsumption and smooth muscle relaxation are
not compatible with the implication only of beta 1 or
beta 2 receptors. Harms HH et al., in 1977, issued the
hypothesis of the existence of some “atypical”
receptors, by describing them on the white adipocytes of
rats [2]. In the same way, atypical beta-receptors are
implicated in the mediation of insulin secretion [3, 4]
and in the relaxation of thedigestive tract [5–7].
Tan S and Curtis-Prior PB proposed, in 1983, that the
beta-receptors existent on the white adipocytes would
be called beta 3 [8].
The major proof for the existence of beta 3 receptors
was given by Arch JR et al., in 1984, by reporting that a
serial of new beta adrenergic ligands (BRL 26830A,
BRL 33725A, BRL 35135A), which were not specific
ligands on classical beta-receptors,had remarkable
anti-obesity actions on mice with severe obesity
and diabetes [9]. The beta 3 receptor was cloned by
Emorine LJ et al. in 1989 [10].

Methods
of
identification
and
characterization
of
adrenergic
receptors’ structure and localization
Adrenergic receptors are membranous proteins.
The discovery of the genes that encode membranous
proteins was made by identifying some nucleotidesequences in the structure of these genes, which
correspond to some hydrophobic amino acids (the
transmembrane portions of these proteins). Later on,
using the technique for obtaining cDNA (complementary DNA), these proteins were synthesized on some
microorganisms in several steps:
▪ attainment of a precursor of mRNA by the aid of
DNA-dependent RNA-polymerase following the
nucleotide sequence of amembrane protein;
▪ removal of introns and obtainment of mRNA;
▪ synthesis of a single-chain DNA on the model of
RNA by the aid of a reverse transcriptase;
▪ obtainment of double-chain DNA by coupling the
nitrogen bases of single-chain DNA, which will be
introduced in the prokaryote cell. This cell will
synthesize the requested protein using its own enzymes
for transcription and translation.
Membranous...