Gastrin-releasing peptide receptor (Gastrin_pep_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Bombesins are peptide neurotransmitters whose biological activity resides in a common C-terminal sequence, WAXGHXM. In the periphery, bombesin-related peptides stimulate smooth muscle and glandular secretion. In the brain, these peptides are believed to play a role in homeostasis, thermoregulation and metabolism, and have been reported to elicit analgesia and excessive grooming, together with central regulation of a variety of peripheral effects.

Mammalian bombesins are encoded by 2 genes. The preproGRP gene transcript encodes a precursor of 147 amino acids, which gives GRP and GRP18-27. The preproNMB gene transcript encodes a precursor of 117 amino acids, which is metabolised to neuromedin B. Receptors for these peptides have widespread distribution in peripheral tissue. High levels are found in smooth muscle and in the brain.

The gastrin-releasing peptide receptor has a wide distribution in peripheral tissue. High levels are found in smooth muscle (e.g., intestine, stomach and bladder) and in secretory glands (e.g., pancreas). In the brain, it is found in high levels in the hypothalamus, and is present in other areas in lower levels (e.g., the olfactory tract, dendate gyrus and cortex). It is also found in various cell lines (e.g., Swiss 3T3 fibroblasts and small-cell lung carcinomas). GRP receptors activate the phosphoinositide pathway via a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class.