Receptors for gut regulatory peptides.
Receptors for regulatory peptides (hormones or neurotransmitters) play a pivotal role in the ability of cells to taste the rich neuroendocrine environment of the gut. Recognition of low concentration of peptides with a high specificity and translation of the peptide-receptor interaction into a biological response through different signalling pathways (adenylyl cyclase-cAMP or phospholipase C-phosphatidylinositol) are crucial properties of receptors. While many new receptors have been identified and thereafter characterized functionally during the 1980s, molecular biology now emerges as the privileged way for the structural characterization and discovery of receptors. Different strategies of receptor cloning have been developed which may or may not require prior receptor purification. Among cloning strategies that do not require receptor purification, homology screening of cDNA libraries, expression of receptor cDNA or mRNA in Xenopus laevis oocytes or in COS cells, and the polymerase chain reaction method achieved great success, e.g. cloning of receptors for cholecystokinin, gastrin, glucagon-like peptide 1, gastrin-releasing peptide/bombesin, neuromedin K, neuropeptide Y, neurotensin, opioids, secretin, somatostatin, substance K, substance P and vasoactive intestinal peptide. All these receptors belong to the superfamily of G-protein-coupled receptors which consist of a single polypeptide chain (350-450 amino acids) with seven transmembrane segments, an N-terminal extracellular domain and a C-terminal cytoplasmic domain. In this chapter, we have detailed the properties of three receptors which play an important role in digestive tract physiology and illustrate various signal transduction pathways: pancreatic beta-cell galanin receptors which mediate inhibition of insulin release and intestinal epithelial receptors for vasoactive intestinal peptide and peptide YY, which mediate the stimulation and inhibition of water and electrolyte secretion, respectively.
Laburthe
M
M
Inserm V239, Faculté de Médecine, Bichat, Paris, France.
Couvineau
A
A
Amiranoff
B
B
Voisin
T
T
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D019004:Galanin; D006801:Humans; D019894:Peptide YY; D010455:Peptides / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D010455:Peptides; D010716:Phosphatidylinositols; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D019894:Peptide YY; D014660:Vasoactive Intestinal Peptide; D019004:Galanin; D000242:Cyclic AMP