RT Journal Article
SR Electronic
T1 Optical approaches for investigating neuromodulation and G Protein-Coupled Receptor signaling
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP PHARMREV-AR-2022-000584
DO 10.1124/pharmrev.122.000584
A1 Marcus, David J
A1 Bruchas, Michael R.
YR 2023
UL http://pharmrev.aspetjournals.org/content/early/2023/07/10/pharmrev.122.000584.abstract
AB Despite that fact roughly 40% of all FDA approved pharmacological therapeutics target G Protein-Coupled Receptors (GPCRs), there remains a noted gap in our understanding of the physiological and functional role of these receptors at the systems level. While heterologous expression systems and in vitro assays have revealed a tremendous amount about GPCR signaling cascades, how these cascades interact across cell types, tissues, and organ systems remains obscure. Classic behavioral pharmacology experiments lack both the temporal and spatial resolution to resolve these long-standing issues. Over the past half century, there has been a concerted effort toward the development of optical tools for understanding GPCR signaling. From initial ligand uncaging approaches to more recent development of optogenetic techniques, these strategies have allowed researchers to probe longstanding questions in GPCR pharmacology both in vivo and in vitro. These tools have been employed across biological systems and have allowed for interrogation of everything from specific intramolecular events to pharmacology at the systems level in a spatiotemporally specific manner. In this review, we present a historical perspective on the motivation behind and development of a variety of optical toolkits that have been generated to probe GPCR signaling. In particular, we highlight how these tools have been utilized in vivo to uncover the functional role of distinct populations of GPCRs and their signaling cascades at a systems level. Significance Statement G Protein-Coupled Receptors remain the most targeted class of proteins for pharmaceutical compounds, yet we still have a limited understanding of how their unique signaling cascades effect physiology at the systems level. In this review, we discuss a vast array of optical techniques that have been devised to probe GPCR signaling both in vitro and in vivo.