**Abstract**

The G-protein-coupled receptors (GPCRs, also called seven-transmembrane receptor, 7TMRs, or heptahelical receptor) are a conserved family of seven transmembrane receptors which are essential not only in the healthy heart and blood vessels but also in for treatment and therapy of cardiovascular disease and failure. Heart failure is a global leading cause of morbidity and death and as such understanding 7TMRs, their functions, structures and potential for therapy is essential. This review will investigate the roles of the receptors in the healthy functioning cardiovascular system, and in cardiac disorders with an emphasis in cardiomyopathy. It will also explore the role of autoimmunity and autoantibodies against the G-protein-coupled receptors in cardiomyopathy.

**Keywords:** angiotensin, adrenoreceptors, cardiomyopathy, heart disease, endothelin-1, muscarinic receptors, vascular

## **1. Introduction**

The 7 transmembrane receptors (7TMRs) also known as G-protein coupled receptors (GPCRs) constitute the largest family of plasma membrane receptors. The superfamily of 7TMRs includes receptors for hormones, neurotransmitters and ion channels, and is critical to mediate physiological and cellular processes [1, 2].

Composed of seven transmembrane hydrophobic alpha (α) helices joined by three intracellular and three extracellular loop structures, a cytoplasmic carboxyl terminus and an extracellular amino terminus (**Figure 1**), 7TMRs signal by stimulating heterotrimeric G proteins following the presentation of an agonist to the receptor [3]. Agonist binding at the 7TMR extracellular region initiates the formation of a G protein. Guanosine diphosphate (GDP) is released from the G protein in exchange for guanosine triphosphate (GTP). The GTP bound α subunit disassociates from the βγ dimer, both of which activate several effectors such as adenylyl cyclase, phospholipases and ion channels [3]. The Gα subunit can be categorised in

**Figure 1.**

*General structure of a seven transmembrane receptor (7TMR)/G protein coupled receptor (GPCR). Extracellular loops 1–3 (EL1–3) and intracellular loops (IL1–3) connecting the 7 transmembrane helices (TM1–7). NH2▬N-terminal chain and COOH▬C-terminal chain.*

to sub groups Gαs, Gαi, Gαq/11 and Gα12/13 [3]. The Gα subunits and the Gβγ dimer deriving from the heterotrimeric G protein can combine with downstream effector molecules such as adenylyl cyclase or phospholipase C to control cellular signalling pathways involving secondary messengers [3]. Examples of secondary messengers include cyclic adenosine monophosphate (cAMP), inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) which elicit cellular and physiological responses [4].
