Info

49,600 4

85,000 500-1000

GI tract

To stimulate (i) gallbladder contraction; (ii) secretion of enzymes from ancinar pancreas

452 48,900 4

95,000 3-10

Brain and spinal cord (CNS) Modulate anxiety Neuroleptic activity

" The information in this table describes properties of cloned rat CCK-A and CCK-B receptors. [Abstracted from Wank, S. A., Harkins, R., Jensen, R. T., et al. (1992). Purification, molecular cloning, and functional expression of the cholecystokinin receptor from rat pancreas. Proc. Natl. Acad. Sci. USA 89, p 3125-3129; and from Wank, S. A., Pisegna, J. R., and DeWeerth, A. (1992). Brain and gastrointestinal cholecystokinin receptor family: Structure and functional expression. Proc. Natl. Acad. Sci. USA 89, 8691-8695.]

The principal biological response of secretin is to stimulate the secretion of bicarbonate and water by the acinar cells of the pancreas. This response is stimulated by ligand occupancy of the secretin receptor, which is located on the outer cell membrane of the pancreatic acinar cells. The human secretin receptor has been cloned and found to be a 419-amino acid peptide (47,900 molecular weight) that belongs to the family of G protein-coupled receptors with seven transmembrane domains. Other members of the receptor family include VIP, glucagon-like peptide (GLP-1), parathyroid hormone (PTH), and calcitonin (CT). The mature receptor protein contains 5 potential sites for asparagine-linked glycosylation as well as 10 cysteines for disulfide formation. The human secretin receptor has 48% homology with the human VIP receptor.

The biological effects of secretin are believed to occur via receptor-mediated stimulation of adenylate cyclase, which leads to the secretion of bicarbonate and H20 by the acinar cells.

E. Enkephalins

There is direct evidence of the biosynthesis of both Met-enkephalin and Leu-enkephalin within the myenteric neurons of the gut. As summarized in Figure 19, the enkephalins are produced as a consequence of processing of the proopiomelanocortin mRNA. In addition, a second gene has been found in the gut that codes for precursor molecules of Leu-enkephalin and Met-enkephalin. Each of the enkephalins consists of five amino acids (Tyr-Gly-Gly-Phe-X), and they differ only at the COOH residue where X may be either Leu or Met. The biological actions of the enkephalins in the gut are not understood in detail. Their principal effects are to inhibit gut motility and mucosal secretions while stimulating sphincter tone.

F. Enteroglucagon

The topic of enteroglucagon is covered in Chapter 7. Enteroglucagon, also known as glicentin, represents a larger form of the pancreatic 29-amino-acid glucagon. The structures are contained within the 160-amino-acid proglucagon sequence: enteroglucagon consists of 69 amino acids (see Figure 8-6). Enteroglucagon is biosynthesized in the mucosal L cells. Enteroglucagon has been postulated to be a trophic factor for the intestinal mucosa.

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