Ghrelin (; or lenomorelin, INN) is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid. Ghrelin activates cells in the anterior pituitary gland and hypothalamic arcuate nucleus, including neuropeptide Y neurons that initiate appetite. Ghrelin stimulates brain structures having a specific receptor – the growth hormone secretagogue receptor 1A (GHSR-1A). Ghrelin also participates in regulation of reward cognition, learning and memory, the sleep-wake cycle, taste sensation, reward behavior, and glucose metabolism. History and name Ghrelin was discovered after the ghrelin receptor (called growth hormone secretagogue type 1A receptor or GHS-R) was determined in 1999. The hormone name is based on its role as a growth hormone-releasing peptide, with reference to the Proto-Indo-European root gʰre-, meaning "to grow". Gene, transcription products, and structure The GHRL gene produces mRNA which has four exons. Five products arise: the first is the 117-amino acid preproghrelin. It is homologous to promotilin; both are members of the motilin family. It is cleaved to produce proghrelin which is cleaved to produce an unacylated 28-amino acid ghrelin and an acylated C-ghrelin. Obestatin is presumed to be cleaved from C-ghrelin. Ghrelin only becomes active when caprylic (octanoic) acid is linked posttranslationally to serine at the 3-position by the enzyme ghrelin O-acyltransferase (GOAT) to form a proteolipid. It is located on the cell membrane of ghrelin cells in the stomach and pancreas. The non-octanoylated form is desacyl ghrelin. It does not activate the GHS-R receptor but does have other effects: cardiac, anti-ghrelin, appetite stimulation, and inhibition of hepatic glucose output. Side-chains other than octanoyl have also been observed: these can also trigger the ghrelin receptor. In particular, decanoyl ghrelin has been found to constitute a significant portion of circulating ghrelin in mice, but as of 2011 its presence in humans has not been established. Ghrelin cells Alternative names The ghrelin cell is also known as an A-like cell (pancreas), X-cell (for unknown function), X/A-like cell (rats), Epsilon cell (pancreas), P/D sub 1 cell (humans) and Gr cell (abbreviation for ghrelin cell). Location Ghrelin cells are found mainly in the stomach and duodenum, but also in the jejunum, lungs,