What question did this study set out to answer?

To characterize and compare the pharmacological binding profiles and intracellular signaling mechanisms of rat AT1a and AT1b angiotensin receptor subtypes expressed in adrenocortical Y-1 cells.

May 1, 1996AJP Endocrinology and Metabolism

Properties of AT1a and AT1b angiotensin receptors expressed in adrenocortical Y-1 cells

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Population

Adrenocortical Y-1 cells stably transfected with the AT1a and AT1b subtypes of the rat angiotensinIIAT1…

Comparison

Angiotensin II and various antagonists vs Comparison between AT1a and AT1b receptor subtypes

Design

Preclinical

Authors

YTYing TianShanghai Jiao Tong University ABAlbert J. BaukalNational Institutes of Health KSKathryn SandbergGeorgetown University

Discussion

Member takes

Implication

Minor AT1a/AT1b binding differences may guide subtype-selective ligand design; leaves open relevance to human physiology or cardiovascular outcomes.

Key Points

To characterize and compare the pharmacological binding profiles and intracellular signaling mechanisms of rat AT1a and AT1b angiotensin receptor subtypes expressed in adrenocortical Y-1 cells.
Stably transfected murine adrenocortical Y-1 cells with rat AT1a or AT1b receptor cDNA clones.
Performed competitive ligand binding assays with native ANG II, peptide antagonists, and losartan, combined with photoaffinity labeling and pertussis toxin sensitivity tests.
Measured intracellular signaling responses, including inositol phosphate formation, cytoplasmic Ca2+ levels, and forskolin-stimulated cAMP accumulation.
Both receptor subtypes bound ANG II and [Sar1,Ile8]ANG II with comparable affinities, but AT1b showed higher affinity than AT1a for losartan (IC50 4.7 nM vs 9.7 nM), ANG III (33 nM vs 126 nM), and [Sar1,Gly8]ANG II (1.2 nM vs 6.2 nM).
ANG II stimulated inositol phosphate formation and elevated cytoplasmic Ca2+ in both AT1a- and AT1b-expressing cells via Gq/G11 coupling, insensitive to pertussis toxin.
Neither AT1a nor AT1b receptors effectively inhibited forskolin-induced cAMP accumulation, demonstrating an absence of Gi coupling and adenylate cyclase inhibition.

Structured PICO

Population

Adrenocortical Y-1 cells stably transfected with the AT1a and AT1b subtypes of the rat angiotensin (ANG)IIAT1 receptor cDNA

Intervention

Angiotensin II and various antagonists (losartan, ANG III, [Sar1,Ile8]ANG II, [Sar1,Gly8]ANG II)

Comparator

Comparison between AT1a and AT1b receptor subtypes

Outcome

Pharmacological binding affinities and functional properties (inositol phosphate formation, cytoplasmic Ca2+ levels, cAMP accumulation)surrogate

AT1a and AT1b receptors exhibit small differences in binding pharmacology but share similar Gq/G11 coupling to the phosphoinositide-Ca2+ signaling pathway without Gi coupling in murine adrenal tumor cells.

Cite This Study

Tian et al. (1996) studied this question.

synapsesocial.com/papers/6a8ad9bdf19228bbb2fb3a6f https://doi.org/10.1152/ajpendo.1996.270.5.e831

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Implication

Minor AT1a/AT1b binding differences may guide subtype-selective ligand design; leaves open relevance to human physiology or cardiovascular outcomes.

Properties of AT1a and AT1b angiotensin receptors expressed in adrenocortical Y-1 cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Properties of AT1a and AT1b angiotensin receptors expressed in adrenocortical Y-1 cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider