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(Circulation Research. 2003;92:342.)
© 2003 American Heart Association, Inc.

Editorials

A Magnificent Time With the "Magnificent Seven" Transmembrane Spanning Receptors

Robert J. Lefkowitz

From the Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC.

Correspondence to Robert J. Lefkowitz, MD, Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Box 3821, Duke University Medical Center, Durham, NC 27710. E-mail Lefko001@receptor-biol.duke.edu

Key Words: transmembrane spanning receptors • G protein–coupled receptor kinase 2 • receptor genes

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The largest, most ubiquitous, and most versatile of the receptor gene families is that which encodes the seven transmembrane spanning receptors. In the cardiovascular system, such receptors regulate, for example, the rate and force of cardiac contraction, peripheral arterial resistance, and various aspects of renal function. The larger superfamily of receptors also regulates everything from sensory perception (vision, smell, taste) to hormonal and neurotransmitter signaling, to immune functions such as chemotaxis. There is virtually no area of human physiology in which they are not implicated. A majority of prescription drugs sold target such receptors either directly or indirectly. In the field of cardiovascular medicine, this is exemplified by - and ß-adrenergic receptor agonists and antagonists, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors.

A profound alteration in our understanding of these receptors occurred during the 1970s and 1980s, which transformed everything from the way they are viewed, to how they are studied, to how new drugs are discovered. I provide here a very personal recollection and perspective of my own voyage of discovery during this time, of its scientific antecedents, and of the technical and conceptual barriers that needed to be scaled.

The notion that biologically active substances initiate their actions by binding with high affinity and selectivity to some "receptive substance" on cells dates back about a hundred years. Early work of Ehrlich on interactions of antigens with cells and of chemotherapeutic agents with their targets was made even more explicit by J.N. Langley and H.H. Dale who, during the . . . [Full Text of this Article]

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