The Ghrelin Receptors (GHS-R1a and GHS-R1b)

Abstract

The growth hormone (GH) secretagogue receptor (GHS-R1a) is a G protein-coupled receptor (GPCR) expressed in the brain as well as other areas of the body. In the early 1990s, this receptor was expression cloned in MERCK laboratories by using a group of synthesized small molecules known to increase GH release in humans and other animals. Since its discovery, hundreds of studies have shown the importance of this receptor and its endogenous ligand, ghrelin, in metabolism, neurotransmission, and behavior. Even more relevant are the prospective benefits that will result from pharmacologic manipulation of GHS-R1a. Multiple GHS-R1a agonists and antagonists are available for experimentation, and some have been used in patients with promising results. Studies in rodents have revealed intriguing potential roles for GHS-R1a modulation. Our goal in this chapter is to connect these studies with the inherent advantages of targeting this receptor pharmacologically.

Ghrelin suppresses Purkinje neuron P-type Ca2+ channels via growth hormone secretagogue type 1a receptor, the βγ subunits of Go-protein, and protein kinase A pathway

“…GHS-R1a is the functional receptor for ghrelin in vivo [2,10]. To determine whether GHS-R1a participates in the I Ba responses to ghrelin, we first characterized the mRNA and protein expression of GHS-R1a in rat cerebellum by RT-PCR and western blot, respectively.…”

“…Two growth hormone secretagogue receptor (GHS-R) subtypes, generated by alternative splicing of a single gene, have so far been identified as the endogenous receptors for ghrelin: the full-length type 1a receptor (GSH-R1a) and the truncated GHS-R1b [2,3]. GHS-R1a is the fully-functional form of the receptor.…”

“…In contrast, GHS-R1b lacks transmembrane domains 6 and 7, and is devoid of high-affinity ligand-binding and signal transduction capacities [4,5]. GHS-R1a is widely expressed in the brain and in peripheral tissues, including the heart, pancreas, and testis [2,5,6]. Ghrelin's actions through GHS-R1a have been implicated in regulating a variety of physiological processes, including stimulation of growth hormone release, modulation of glucose metabolism, enhancement of learning and memory, and energy balance [5].…”

“…Recently, it has also been speculated that ghrelin may have a physiological function in the cerebellum [7]. Some reports have suggested that ghrelin receptors modulate the activity of cerebellar circuits and may contribute to the control of motor behaviour [2,5,8]. Ghrelin-immunopositive cells have been localized in the cerebellum, particularly in the Purkinje cell layer, and widespread distribution of GHS-R mRNA in the cerebellar cortex has also been reported [7,9,10].…”

Ghrelin As An Ontogenetic Factor And A Gastrointestinal Hormone In The Prenatal And Postnatal Period In Rat

“…Through the use of Bioluminescence Resonance Energy Transfer (BRET), heterodimers of GHS-R1А and GHS-R1В are shown during a process of oligomerisation in the endoplasmic reticulum of isolated subcellular fractions [38]. GHS-R1А is a mature polypeptide of 366 amino acid sequences and 5 transmembrane domains [39]. DOI: 10.9790/0853-1603107790 www.iosrjournals.org 79 | Page…”