Gastrin and Cholecystokinin

Discovery of gastrin, the continued doubt about its existence were mentioned in the introductory part of this chapter. These doubts were laid to rest with the isolation of the hormone, determination of its amino acid sequence and synthesis. Gastrin is an acidic 17-peptide with pyroglutamic acid at the N-terminus and with not less than five glutamic acid residues, in a row, in its chain. Two variants were isolated, (porcine) gastrin I 

Pyr-Gly-Pro-Trp-Met-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 and gastrin II in which the hydroxyl group of the tyrosine residue is esterified with sulfuric acid. 

The two Lys residues, in positions 16 and 17, are the signal for the specific enzyme that cleaves the chain to produce the 17-peptide gastrin. 

As early as in 1856 the observation was made by Claude Bernard that introduction of hydrochloric acid into the duodenum causes the flow of bile. In the nineteen-twenties, Ivy and his coworkers proved the presence of cholecystokinin in intestinal extracts, but the gall bladder contracting hormone was isolated, from hog intestines, only several decades later, by the efforts of J.E. Jorpes and V. Mutt (Plate 23) [2] who concluded their study with the elucidation of the structure [115]. The 33-residue sequence of cholecystokinin (CCK, porcine). 

Synthesis of CCK was attempted in several laboratories and while hormonally active highly potent preparations with the C-terminal sequence of the 

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TEMLER R s, METTRAUX c (1986) Gastrin and cholecystokinin levels in rats fed soya bean trypsin inhihitor. Adv Exp Med Biol. 199 133—41. 

Marley PD, Rehfeld JF, Emson PC Distribution and chromatographic characterisation of gastrin and cholecystokinin in the rat central nervous system. J Neurochem 42 1523-1535, 1984... 

Know the action of hormones involved in the digestion and metabolism of food substances insulin, glucagon, secretin, gastrin, and cholecystokinin. Know their chemical and physiologic properties and what controls their blood levels. 

Gastrin and cholecystokinin receptor ligands consisting of lH-imidazole-4-yl-benzooxazole derivatives, (II), prepared by Kalindjian (3) were effective in controlling excess gastric acid secretion. 

The five C-terminal amino acids of gastrin and cholecystokinin are identical, which explains their overlapping biological effects. 

Bombesin is a tetradecapeptide amide. It is a peptidehormone which activates a G protein-coupled receptor and causes release of gastrin and cholecystokinin in the intestine. 

The role of gastrin and cholecystokinin in tumors of gastrointestinal tract is reported by Lamers and Jansen [53]. Elevation of cytosolic calcium in SCLC by cholecystokinin has also been reported [54]. 

Fig. 1. The C-terminal structure of members of the gastrin family. The members are characterized by the same active site, i.e., the C-terminal tetrapeptide amide (shown in the internal box). Another characteristic is an O-sulfated tyrosyl residue close to the active site. In gastrin peptides the sulfated tyrosyl residue is located in position six (as counted from the C-terminus) in cholecystokinins it is position seven. The frog skin peptide caerulein therefore acts as cholecystokinin in mammals. Cionin is a neuropeptide from the protochordate, Ciona intestinalis. Cionin is unique in having O-sulfated tyrosyl residues in both positions six and seven. The cionin structure is therefore likely to correspond to that of the common ancestor of gastrin and cholecystokinin.

The first sulfakinins were again isolated from whole heads of L. maderae and its sequence elucidation suggested that this family is structurally related to the mammalian peptide family comprising gastrin and cholecystokinin [151]. Its biological activity was measured by stimulation of contractions of the cockroach hindgut. Later, members of this family... 

Gastrin family, a member of the gastroen-teropancreatic peptide families. This family comprises the mammalian hormones gastrin and cholecystokinin, the pro-tochordean neuropeptide cionin, and... 

Several amino-acids are important neurotransmitters in the c.n.s. Glutamic and aspartic acids seem to be excitatory transmitters in the entire brain. y-Aminobutyric acid (GABA) and glycine are important inhibitory transmitters, the former in supraspinal interneurons and the latter at spinal interneurons (Curtis and Johnston, 1970). Of the polypeptide neurotransmitters, the most studied have been the endorphins and enkephalins (see Section 12.8), Substance P (an undecapeptide that helps transmit the sense of pain (von Euler and Pernow, 1977, somatostatin, and gastrin, and cholecystokinin whose action in the gut has been well researched. For more on GABA, see Section 12.7. 

Somatotropin release inhibiting hormone (SIH), somatostatin a polypeptide, M, 1638, which inhibits secretion of somatotropin, thyrotropin, insulin, glucagon, gastrin and cholecystokinin. SIH has a broad activity spectrum it acts outside the hypothalamus as a neurotransmitter in the central nervous system, and as a hormone in the intestinal tract it has also been found in the thyroid and pancreas. 

Luttichau HR, Van Solinge WW, Nielsen FC, Rehfeld JF (1993) Developmental expression of the gastrin and cholecystokinin genes in rat colon. Gastroenterology 104 1092-1098... 

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