Gastrointestinal & Liver by Feldman - Sleisenger & Fordtran
By Feldman - Sleisenger & Fordtran
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8 Clinically, CCK has been used together with secretin to stimulate pancreatic secretion for pancreatic function testing. It is also used radiographically or by nuclear medicine physicians to evaluate gallbladder contractility. There are no known diseases of CCK excess. Low CCK levels have been reported in bulimia nervosa and in individuals with celiac disease who have reduced intestinal mucosal surface area.   Elevated levels of CCK have been reported in some patients with chronic pancreatitis, presumably owing to reduced pancreatic enzyme secretion and interruption of negative feedback regulation of CCK release.
The inhibitory action of somatostatin is consistent with a role in causing muscle relaxation in advance of a peristaltic wave. The abundance of VIP in the myenteric plexus also suggests that its inhibitory actions are important for smooth muscle relaxation in gut motility. VIP neurons that project from the submucosal plexus to the mucosa most likely stimulate intestinal fluid secretion. Other neurons that innervate the mucosa contain acetylcholine. Mucosal cells of the intestine contain receptors for both VIP and acetylcholine, allowing these transmitters to exert synergistic effects, because VIP increases intracellular cyclic adenosine monophosphate (cAMP) levels and acetylcholine increases intracellular calcium in the target cell.
These receptors share 55% to 65% sequence homology and often the presence of a D-R-Y (Asp-Arg-Try sequence) motif in the second intracellular loop. Class II receptors include the secretin/glucagon/VIP family. This group is distinct from class I receptors, sharing only approximately 12% sequence homology with class I and the absence of the D-R-Y motif. Class III GPCRs contain the metabotrophic receptors (calcium-sensing and glutamate receptors). TABLE 1-2 -- Classification of G ProteinCoupled Receptors Class I Rhodopsin, catecholamines, acetylcholine, serotonin, angiotensin, gastrin, cholecystokinin, neuropeptide Y, substance P, endothelin, opioid, chemokine, histamine, vasopressin Class II Secretin, calcitonin, parathyroid hormone, vasoactive intestinal polypeptide, glucagon, glucagon-like peptide 1, pituitary adenylate cyclaseactivating peptide Class III Glutamate-metabotrophic receptors, calcium receptors GPCRs contain an extracellular amino terminus and an 12 intracellular carboxyl terminus ( Fig.