CCK-4 receptors

Two CCK receptor subtypes, CCK and CCKg are known. A related receptor, the gastrin receptor, has also been described. CCK receptors predominate in the gastrointestinal tract and pancreas and are also localized in discrete brain regions. CCKg receptors predominate in the brain. A 71623... 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

Wank, S. A., G protein-coupled receptors in gastrointestinal physiology. I. CCK receptors an exemplary family, Am. J. Physiol. 1998, 274, G607-G613... 

Control of feeding behavior involves peripheral peptides (insulin, ghrelin, leptin) plus several peptides in the CNS (orexins/hypocretins, CCK, galanin, MSH, neuropeptide Y, CRH, cocaine-and-amphetamine-regulated transcript (CART)) [35, 36]. Some of the same peptides are involved in reward systems crucial to drug addiction. Specific receptor blockers are being tested for many of these peptide-receptor systems, with the hope of very selective actins with minimal side effects [35], For example, there are two CCK receptor subtypes, CCK-A and... 

Miller reported several monomeric, photolabile CCK agonists and antagonists. The photoreactive residue (L-Bpa) was placed at the N-terminal and a fluorescent reporter group was also linked to it. The CCK receptor in the study was expressed on Chinese hamster ovary-CCKR cells. To identify the labeled domains on the receptor capillary electrophoresis was used with laser induced fluorescence detection. Separate regions were labeled with the two photoprobes, one labeled the first extracellular loop (96-121), while the other probe labeled a fragment in the second extracellular loop (174-195). 

CCK-receptor binding (ICso nM) (l I]CCK-8) Opioid binding (ICso nM)... 

CCK receptors SCLC, pancreatic cancers, neuroblastomas, meningiomas, medullary thyroid carcinomas... 

Cholecystokinin (CCK) is one of the brain-gut peptides. Its most abundant form in the brain is the C-terminal sulphated octapeptide fragment CCK8, which interacts with the same affinity with both CCK receptor subtypes, CCK-A and CCK-B. Extensive pharmacological studies have been carried out over the last few years suggesting that CCK may participate in the neuroendocrine responses to stress (Harro et al 1993 Dauge and Lena 1998). Interestingly, CCK8 and CRH are co-locahzed in neurons of the hypothalamic PVN (Mezey etal. 1985). 

A gastrinlike neuropeptide, CCK exists in the central nervous system both as an octapeptide [CCK-8] and as a tetrapeptide (CCK-4) (Rex et al. 1994b). The octapeptide CCK-8 occurs predominantly in sulfated form and is one of the most abundant neuropeptides in the central nervous system (Rex et al. 1994b]. Two major subtypes of CCK receptors, labeled as CCK-A and CCK-B receptors, have been identified (Hill et al. 1993]. At this point, the most promising neuropeptide receptor to target for the treatment of anxiety may be the CCK-B receptor. This receptor is widely distributed throughout... 

Pandya PK, Huang SC, Talkad VD, et al Biochemical regulation of the three different states of the cholecystokinin (CCK) receptor in pancreatic acini. Biochim Biophys Acta 1224 117-126, 1994... 

Cholecystokinin (CCK) The tetrapeptide CCK causes more panic attacks when infused into patients with panic disorder than it does in normal volunteers, which suggests increased sensitivity of the brain type of CCK receptor, known as CCK-B. Unfortunately, in early investigations CCK-B antagonists did not appear to be effective for panic disorder. Nevertheless, agents with novel pharmacological mechanisms of action are sometimes evaluated for their potential antipanic actions by testing whether they can block CCK-induced panic attacks. 

Cholecytokinin ligands - agonists of the central CCK receptors cause anxiety and precipitate panic attacks in predisposed individuals. Two types of CCK receptors have been identified, CCK-A and -B (from the alimentary tract and brain respectively), both of which occur in the mammalian brain. CCK-B agonists initiate anxiety while the antagonists are anxiolytic in both experimental and clinical situations. So far the poor bioavailability and side effects have limited their clinical development. 

Although the mechanisms through which enhanced opioid activity may occur are not known, a complex interaction among p-opioid, 5-opioid, and chole-cystokinin (CCK) receptors has been proposed [153,162]. A basis for such interactions may lie in reports that CCK antagonizes morphine antinocicep-... 

Niederau et al. (1989) compared the effects of CCK receptor antagonists on rat pancreatic secretion in vivo. Output of amylase in pancreatico-biliary secretion was measured after various doses of caerulein. The effects of high caerulein doses were dose-dependent inhibited by CCK-antagonists. 

Lin TM, Karvinen E, Ivy AC (1957) Role of pancreatic digestion in cholesterol absorption. Am J Physiol 190 214-220 Niederau M, Niederau G, Strohmeyer G, Grendell JH (1989) Comparative effects of CCK receptor antagonists on rat pancreatic secretion in vivo. Am J Physiol (Gastrointest Liver Physiol) 19 G150... 

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