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Alpha 1-adrenergic receptor subtypes

K P Minneman¹, T A Esbenshade

¹Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.

Annual Review of Pharmacology and Toxicology

|January 1, 1994

Summary

Understanding alpha 1-adrenergic receptor (AR) subtypes remains challenging due to ongoing debate about their exact number and signaling. Further research is needed to clarify these receptors for potential therapeutic advancements.

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Area of Science:

Pharmacology
Molecular Biology
Adrenergic Receptor Research

Background:

There is no consensus on the number and signaling mechanisms of alpha 1-adrenergic receptor (AR) subtypes.
Pharmacological studies distinguish two native subtypes (alpha 1A and alpha 1B), while molecular cloning has identified three subtypes (alpha 1B, alpha 1C, and alpha 1D).
The precise relationship between cloned receptors and native subtypes is unclear, with the alpha 1A subtype likely not yet cloned.

Purpose of the Study:

To clarify the number and properties of alpha 1-adrenergic receptor (AR) subtypes.
To understand the relationship between cloned receptors and native subtypes.
To define the drug specificities and second messenger pathways of alpha 1-AR subtypes.

Main Methods:

Molecular cloning of complementary DNA sequences for remaining alpha 1-AR subtypes.
Pharmacological characterization of receptor subtypes.
Investigation of cellular and tissue distribution, developmental profiles, and functional importance.

Main Results:

Current data suggest the pharmacologically defined alpha 1A subtype has not yet been cloned.
Discrepancies exist between pharmacologically identified and cloned alpha 1-adrenergic receptor (AR) subtypes.
Significant knowledge gaps remain regarding the distribution and function of alpha 1-AR subtypes.

Conclusions:

Clarifying the complexity of alpha 1-adrenergic receptor (AR) subtypes is crucial for defining their properties.
Molecular cloning efforts are essential to resolve the number and characteristics of these receptor subtypes.
Selective drugs targeting specific alpha 1-AR subtypes hold therapeutic potential for diseases like benign prostatic hyperplasia, though their impact requires further definition.

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