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(Circulation Research. 2001;88:256.)
© 2001 American Heart Association, Inc.

Editorial

TRP Proteins

Novel Therapeutic Targets for Regional Blood Pressure Control?

William P. Schilling

From the Rammelkamp Center for Education and Research, MetroHealth Medical Center and the Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Correspondence to Dr William P. Schilling, Rammelkamp Center, Room R322, MetroHealth Medical Center, 2500 MetroHealth Dr, Cleveland, OH 44109-1998. E-mail wschilling@metrohealth.org

Key Words: Ca²⁺ channels • store-operated • smooth muscle • adrenergic receptors

	Introduction

 
Peripheral vascular resistance is controlled in large part by the sympathetic branch of the autonomic nervous system. In response to sensory input primarily via the vagus nerve, a change in sympathetic outflow alters the tone of the vascular tree via the release of catecholamines from nerve terminals present in the adventitial layer of the vessel wall and from chromaffin cells of the adrenal medulla. Through action at the ₁-adrenergic receptor (₁-AR) present on the surface of vascular smooth muscle cells (SMCs), catecholamines increase contraction, constrict blood vessels, and, thus, cause an increase in mean arterial pressure.

As in cardiac and skeletal muscle, a rise in cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) triggers contraction of vascular SMCs. Stimulation of ₁-ARs causes an increase in [Ca²⁺]_i through several different mechanisms.^{1 2} First, ₁-AR is a member of the heptahelical receptor family, which activates phospholipase C (PLC) via a GTP-binding protein, G_q. Activation of PLC causes the production of 2 second messengers, inositol-1,4,5-trisphosphate [Ins(1,4,5)P₃] and diacylglycerol (DAG). Ins(1,4,5)P₃ causes the release of Ca²⁺ from the endoplasmic reticulum, resulting in a rapid but transient increase in [Ca²⁺]_i. DAG is primarily thought to activate protein kinase C but may also play a more direct role in activating Ca²⁺ entry (see below). In many types of SMCs, receptor stimulation is associated with activation of nonselective cation channels (NSCCs) that may allow Ca²⁺ to enter the cell from the extracellular space. Perhaps more importantly, the activation of an NSCC will tend . . . [Full Text of this Article]

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