Biomaterial Database

Proglumide peptides and CCK antagonistic action in hog duodenal circular muscle. 1987

I Kimura, and T Kondoh, and M Kimura

New proglumide peptides were synthesized and their inhibitory activity against the cholecystokinin (CCK)-induced relaxation was tested in duodenal circular muscles of hogs in order to locate the active moiety. Isotonic tension is reported as a percentage of the relaxation induced by CCK-4 (4.23 microM) or by Ca-free EGTA (2 mM). In R1-CONHCH(CH2CH2CO-R2)CON(CH2CH2CH3)2, P2-II(R1 = PhCH2O, R2 = Phe33-NH2), its D isomer and P3-I (R1 = Ph, R2 = Asp32-Phe33-NH2) had potent antagonistic activity (IC50 = 47.9 (32.4-72.4) microM, 25.1 (10.0-61.7) microM and 186 (141-240) microM, respectively). Benzotript, from another group of CCK antagonists had an IC50 of 52.5 (40.7-67.6) microM. P2-II (49 microM) or its D isomer (19.6 microM) antagonized non-competitively, and P3-I (168 microM) and benzotript (58.4 microM) antagonized competitively the CCK-4-induced relaxation. P3-I (84 or 168 microM) also antagonized competitively the CCK-8-induced relaxation. The amino acids of Tyr27, Trp30 and Phe33, separately, play important roles for agonist activity for relaxation. Tyr27 is the main relaxing group, Trp30 an antagonistic one and Phe33 is another relaxing one. In the proglumide skeleton, N,N-dipropylglutaramic acid acts like Trp30. Agonist, partial agonist and antagonist activities are exerted by these three groups and bulky substituents.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009126	Muscle Relaxation	That phase of a muscle twitch during which a muscle returns to a resting position.	Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130	Muscle, Smooth	Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)	Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011377	Proglumide	A drug that exerts an inhibitory effect on gastric secretion and reduces gastrointestinal motility. It is used clinically in the drug therapy of gastrointestinal ulcers.	Xylamide,Milid,Xilamide
D011949	Receptors, Cholecystokinin	Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.	CCK Receptors,Caerulein Receptors,Cholecystokinin Octapeptide Receptors,Cholecystokinin Receptors,Pancreozymin Receptors,Receptors, CCK,Receptors, Caerulein,Receptors, Pancreozymin,Receptors, Sincalide,Sincalide Receptors,CCK Receptor,CCK-4 Receptors,CCK-8 Receptors,Cholecystokinin Receptor,Receptors, CCK-4,Receptors, CCK-8,Receptors, Cholecystokinin Octapeptide,CCK 4 Receptors,CCK 8 Receptors,Octapeptide Receptors, Cholecystokinin,Receptor, CCK,Receptor, Cholecystokinin,Receptors, CCK 4,Receptors, CCK 8
D002766	Cholecystokinin	A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety.	Pancreozymin,CCK-33,Cholecystokinin 33,Uropancreozymin
D004386	Duodenum	The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers.	Duodenums
D005260	Female		Females
D005973	Glutamine	A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.	D-Glutamine,L-Glutamine,D Glutamine,L Glutamine