Cholecystokinin

The principal hormones of the human posterior pituitary include the two nonapeptides, oxytocin [50-56-6] and arginine vasopressin [11000-17-2] (antidiuretic hormone, ADH). Many other hormones, including opioid peptides (see Opioids, endogenous), cholecystokinin [9011-97-6] (CCK) (see Hormones, BRAIN oligopeptides), and gastrointestinal peptides, also have been located in mammalian neurohypophysis (6), but are usually found in much lower concentrations (7). Studies have demonstrated that oxytocin and vasopressin are synthesized in other human organs, both centrally and peripherally, and there is considerable evidence for their role as neurotransmitters (see Neuroregulators) (8). 

Newel experimental approaches to anxiety therapy include ligands interacting with the ligand-gated ion channels that are selectively activated by nicotine, C qH 4N2 (87), the well-known active ingredient of cigarettes which has anxiolytic actions (42). Cholecystokinin B receptor ligands, specifically the dipeptoid, CI-988 [130404-91 -0] 02 1142 40 (88) have demonstrated anxiolytic activity ia preclinical models (43). 

The BZ stmcture also has provided a molecular scaffold for a number of peptide receptor ligands (26). Antagonists for the cholecystokinin (CCK-A) receptor, eg, devazepide (65), the thyrotropin-releasing hormone (TRH) receptor, eg, midazolam (66), and the /i -opiate receptor, eg, tifluadom (67), as well as a series of ras famyl transferase inhibitors, eg, BZA-2B (68) (30) have been identified (Table 4). 

CGRP is widely distributed throughout the peripheral and central nervous systems and is found ia sensory neurons and ia the autonomic and enteric nervous systems. In many iastances CGRP is co-localized with other neuroregulators, eg, ACh ia motor neurons, substance P, somatostatin, vasoactive intestinal polypeptide (VIP), and galanin ia sensory neurons. It is also present ia the CNS, with ACh ia the parabigeminal nucleus and with cholecystokinin (CCK) ia the dorsal parabrachial area. CGRP functions as a neuromodulator or co-transmitter. 

Cheng-Prasoff relationship, 65-66, 214 Cholecystokinin receptor antagonists, 80 Cimetidine, 9-10 Clark, Alfred J., 3, 3f, 12, 41 Clark plot, 114 Clearance, 165—166 Clinical pharmacokinetics, 165 Cocaine, 149, 150f Competitive antagonism description of, 114 Gaddum equation for, 101-102, 113,... 

Some amino derivatives 32c-g containing an indolylmethyl substituent were prepared as potential cholecystokinin antagonists by Method A.231... 

Various 1.4-benzodiazepines with a five-membered heteroaromatic ring fused to the 1,2-bond, such as 17, where A represents a heteroaromatic ring, have been prepared by such methods and tested for activity on the central nervous system, as cholecystokinin antagonists and as antagonists of platelet activating factors.245... 

Cholecystokinin (CCK) is produced in the intestine and the brain. It appears to be an important mediator of anxiety. It also stimulates vasopressin secretion and slows gastric emptying. In addition, it is an important humoral satiety signal (appetite control). Various antagonists have been developed and are currently being investigated with regard to their therapeutic potential. 

SB S8 S08.090 TripeptidyI-peptidase 11 Drug target because of cholecystokinin-8 degradation... 

Other peptides that have been linked to the actions of ethanol are corticotropin-releasing factor, urocortin, leptin, cholecystokinin, melanocortins, and galanin (for reviews, see Cowen et al. 2004 Egli 2003 Thiele et al. 2003). 

D Peptides Enkephalins, endorphins, cholecystokinin, substance P (Many others have been implicated)... 

Amino acid receptors Monoamine receptors Lipid receptors Purine receptors Neuropeptide receptors Peptide hormone receptors Chemokine receptors Glycoprotein receptors Protease receptors Metabotropic glutamate and GABAb receptors Adrenoceptors, dopamine and 5-HT receptors, muscarinic and histamine receptors Prostaglandin, thromboxane and PAF receptors Adenosine and ATP (P2Y) receptors Neuropeptide Y, opiate, cholecystokinin VIP, etc. Angiotensin, bradykinin, glucagon, calcitonin, parathyroid, etc. Interleukin-8 TSH, LH/FSH, chorionic gonadotropin, etc. Thrombin... 

Cholecystokinin A and B Anxiogenesis, satiation, Panic, eating disorders,... 

BEGLINGER c, OVERVIEW (2002) Cholecystokinin and eating. Curr Opin Investig Drugs. 3 587-8. 

FURUSE M, YANG s I, MURAMATSU T, OKUMURA J (1990) Enhanced release of cholecystokinin by soya-bean trypsin inhibitor in chickens. Scand J Gastroenterol. 25 1242-6. 

HERZIG K H, BARDOCZ s, GRANT G, NUSTEDE R, FOLSCH u R, PUSZTAi A (1997) Red kidney bean lectin is a potent cholecystokinin releasing stimulus in the rat inducing pancreatic growth. Gut. 41 333-8. 

JAKOB S, MOSENTHIN R, THAELA M J, WESTROM B R, REHFELD J F, OLSEN O, KARLSSON S, AHREN B, OHLSSON A, KARLSSON B w, PIERZYNOWSKI s G (2000) The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin, secretin and cholecystokinin in growing pigs. Arch Tierernahr. 53 273-91. 

JORDINSON M, PLAYFORD R J, CALAM J (1997) Effects of a panel of dietary lectins on cholecystokinin release in rats. Am J Physiol. 273 G946-50. 

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