Growth hormone secretagogue receptor is a G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 that binds ghrelin

Ghrelin

Ghrelin is a 28 amino acid peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone...

 and plays a role in energy homeostasis and regulation of body weight.

Function

Ghrelin is an appetite-regulating factor secreted from peripheral organs that is involved in regulation of energy homoeostasis via binding to the receptor resulting in the secretion of growth hormone by the pituitary gland. The pathway activated by binding of Ghrelin to the Growth hormone secretagogue receptor, GHSR1a, regulates the activation of the downstream mitogen-activated protein kinase

Mitogen-activated protein kinase

Mitogen-activated protein kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.-Activation:MAP kinases are activated...

, Akt

AKT

Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...

, nitric oxide synthase

Nitric oxide synthase

Nitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide from L-arginine. NO is an important cellular signaling molecule, having a vital role in many biological processes...

, and AMPK cascades in different cellular systems. One of the important features of GHSR1a displays constitutive activity possessing basal activity in the absence of an agonist, resulting in a high degree of receptor internalization as well as of signaling activity. Inverse agonists for the ghrelin receptor could be particularly interesting for the treatment of obesity. This activity seems to provide a tonic signal required for the development of normal height, probably through an effect on the GH axis.

Transcripts

Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the Ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for Ghrelin; however, it may function to attenuate activity of isoform 1a.

Selective ligands

A range of selective ligands for the GHSR receptor are now available and are being developed for several clinical applications. GHSR agonists have appetite-stimulating and growth hormone-releasing effects, and are likely to be useful for the treatment of muscle wasting and frailty associated with old-age and degenerative diseases. On the other hand, GHSR antagonists have anorectic

Anorectic

An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...

 effects and are likely to be useful for the treatment of obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

.

Agonists

• Capromorelin
  Capromorelin
  Capromorelin is an investigational medication developed by the Pfizer drug company.It functions as a growth hormone secretagogue and ghrelin mimetic which causes the body to secrete human growth hormone in a way usually seen at puberty and in young adulthood...
  
  
• Hexarelin
• Ipamorelin
• MK-677
  MK-677
  MK-677 is a drug which acts as a potent, orally active growth hormone secretagogue, mimicking the GH stimulating action of the endogenous hormone ghrelin. It has been demonstrated to increase the release of, and produces sustained increases in plasma levels of several hormones including growth...
  
  
• SM-130,686
  SM-130,686
  SM-130,686 is a drug which acts as a potent, orally active growth hormone secretagogue, with around half the potency of the endogenous agonist ghrelin as a stimulator of growth hormone release. It produces dose-dependent increases in muscle mass and decrease in body fat, and is under investigation...
  
  
• Tabimorelin
  Tabimorelin
  Tabimorelin is a drug which acts as a potent, orally active growth hormone secretagogue, mimicking the effects of the endogenous peptide agonist ghrelin as a stimulator of growth hormone release. It was one of the first GH secretagogues developed and is largely a modified polypeptide, but it is...
  
  

External links

• Ghrelin at Colorado State University
  Colorado State University
  Colorado State University is a public research university located in Fort Collins, Colorado. The university is the state's land grant university, and the flagship university of the Colorado State University System.The enrollment is approximately 29,932 students, including resident and...