INVESTIGADORES
MONCZOR Federico
artículos
Título:
Measurement of Inverse Agonism in b-Adrenoceptors
Autor/es:
TAIRA CARLOS; MONCZOR FEDERICO; HÖCHT CHRISTIAN
Revista:
METHODS IN ENZYMOLOGY.
Editorial:
ELSEVIER ACADEMIC PRESS INC
Referencias:
Lugar: New York; Año: 2010 vol. 485 p. 37 - 60
ISSN:
0076-6879
Resumen:
Increasing numbers of compounds, previously classified as antagonists,
were shown to inhibit this spontaneous or constitutive receptor
activity, instead of leave it unaffected as expected for a formal
antagonist. In addition, some other antagonists did not have any effect
by themselves, but prevented the inhibition of constitutive activity
induced by thought-to-be antagonists. These thought-to-be antagonists
with negative efficacy are now known as "inverse agonists." Inverse
agonism at βAR has been evidenced for both subtypes in wild-type GPCRs
systems and in engineered systems with high constitutive activity. It is
important to mention that native systems are of particular importance
for analyzing the in vivo relevance of constitutive activity because
these systems have physiological expression levels of target receptors.
Studies of inverse agonism of β blockers in physiological setting have
also evidenced that pathophysiological conditions can affect
pharmacodynamic properties of these ligands. To date, hundreds of
clinically well-known drugs have been tested and classified for this
property. Prominent examples include the beta-blockers propranolol,
alprenolol, pindolol, and timolol used for treating hypertension, angina
pectoris, and arrhythmia that act on the β₂ARs, metoprolol, and
bisoprolol used for treating hypertension, coronary heart disease, and
arrhythmias by acting on β₁ARs. Inverse agonists seem to be useful in
the treatment of chronic disease characterized by harmful effects
resulting from β₁AR and β₂AR overactivation, such as heart failure and
asthma, respectively.