GASTRIC-INHIBITORY POLYPEPTIDE RECEPTOR, A MEMBER OF THE SECRETIN-VASOACTIVE INTESTINAL PEPTIDE RECEPTOR FAMILY, IS WIDELY DISTRIBUTED IN PERIPHERAL ORGANS AND THE BRAIN

Gastric inhibitory polypeptide (GIP), or glucose-dependent insulinotro pic peptide, is released from endocrine cells in the small intestine a fter meals. It is involved in several facets of the anabolic response and is thought to be particularly important in stimulating insulin sec retion. We have cloned, functionally expressed, and mapped the distrib ution of the receptor for GIP. It is a member of the secretin-vasoacti ve intestinal polypeptide family of G-protein-coupled receptors. When expressed in tissue culture cells, it stimulates cAMP production (EC50 0.3 nm) and also increases intracellular calcium accumulation. GIP re ceptor mRNA is present in the pancreas as well as the gut, adipose tis sue, heart, pituitary, and inner layers of the adrenal cortex, whereas it is not found in kidney, spleen, or liver. It is also expressed in several brain regions, including the cerebral cortex, hippocampus, and olfactory bulb. These results suggest that GIP may have previously un described actions. GIP receptor localization in the adrenal cortex sug gests that it may have effects on glucocorticoid metabolism. Neither G IP nor its effects have been described in the central nervous system, and mRNA for the known peptide ligand for the receptor cannot be detec ted in the brain by in situ hybridization or polymerase chain reaction . This suggests that a novel peptide may be present in the brain.