The distribution of cholecystokinin-8 in the central nervous system of turtles: An immunohistochemical and biochemical study

Immunohistochemical techniques, radioimmunoassay (RIA) and high performance liquid chromatography (HPLC) were used to: (1) determine the regional distribution and amounts of cholecystokinin-8 (CCKS)-like immunoreactivity in the turtle central nervous system, and (2) chemically characterize the CCK8-like material present in the turtle central nervous system. High levels of CCK8-like immunoreactivity were found in the turtle central nervous system, with the highest levels being present in the hypothalamus and neurohypophysis. Moderate levels of the CCK8-like material were found in all other regions of the turtle nervous system except the cerebellum, the olfactory bulbs and the dorsal ventricular ridge of the telencephalon, which contained low levels. The bulk (87%) of the CCK8-like material in turtle central nervous system co-eluted with CCK8-sulfate in gradient elution HPLC. The distribution of CCK8-like immunoreactivity (CCK8LI) observed using immunohistochemistry was consistent with the results of the RIA studies. Numerous CCK8LI-containing neurons and fibers were observed in the hypothalamus and neurohypophysis. Neurons and fibers containing CCK8 were, however, more sparsely distributed outside the hypothalamus. The immunohistochemical data provided evidence for the existence of two major CCK8-containing pathways in turtles that have been previously described in mammals: a pathway from the supraoptic and paraventricular magnocellular nuclei to the external zone of the median eminence and neurohypophysis and a pathway from dorsal root ganglia to the dorsal horn of the spinal cord. Overall, the present results, in conjunction with several previous studies, indicate that CCK8 has had a relatively stable evolutionary history as a CNS neuropeptide among land vertebrates. The molecular structure of CCK8 appears to have been largely (if not entirely) conserved, as has its concentration in many brain regions. A noteworthy exception to such conservatism in the localization of CCK8 is that the concentration of CCK8 in the telencephalon, particularly in the telencephalic cortex, is much lower in turtles than in mammals. The present results therefore suggest that CCK8 may not have become a prominent peptide in the telencephalic cortex (or its anatomical equivalents) until the evolution of neocortex in the mammalian lineage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25605/1/0000152.pd

Cholecystokinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Cholecystokinin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CCK receptors [89]) are activated by the endogenous peptides cholecystokinin-8 (CCK-8), CCK-33, CCK-58 and gastrin (gastrin-17). There are only two distinct subtypes of CCK receptors, CCK1 and CCK2 receptors [63, 123], with some alternatively spliced forms most often identified in neoplastic cells. The CCK receptor subtypes are distinguished by their peptide selectivity, with the CCK1 receptor requiring the carboxyl-terminal heptapeptide-amide that includes a sulfated tyrosine for high affinity and potency, while the CCK2 receptor requires only the carboxyl-terminal tetrapeptide shared by each CCK and gastrin peptides. These receptors have characteristic and distinct distributions, with both present in both the central nervous system and peripheral tissues

Cholecystokinin receptors in GtoPdb v.2023.1

Cholecystokinin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CCK receptors [90]) are activated by the endogenous peptides cholecystokinin-8 (CCK-8), CCK-33, CCK-58 and gastrin (gastrin-17). There are only two distinct subtypes of CCK receptors, CCK1 and CCK2 receptors [64, 124], with some alternatively spliced forms most often identified in neoplastic cells. The CCK receptor subtypes are distinguished by their peptide selectivity, with the CCK1 receptor requiring the carboxyl-terminal heptapeptide-amide that includes a sulfated tyrosine for high affinity and potency, while the CCK2 receptor requires only the carboxyl-terminal tetrapeptide shared by each CCK and gastrin peptides. These receptors have characteristic and distinct distributions, with both present in both the central nervous system and peripheral tissues

The distribution and chromatographic characterization of PHI (peptide histidine isoleucine amide)-27-like peptides in rat and porcine brain

[No abstract available

Aminopeptidase B, a glucagon-processing enzyme: site directed mutagenesis of the Zn2+-binding motif and molecular modelling

<p>Abstract</p> <p>Background</p> <p>Aminopeptidase B (Ap-B; EC 3.4.11.6) catalyzes the cleavage of basic residues at the N-terminus of peptides and processes glucagon into miniglucagon. The enzyme exhibits, <it>in vitro</it>, a residual ability to hydrolyze leukotriene A₄into the pro-inflammatory lipid mediator leukotriene B₄. The potential bi-functional nature of Ap-B is supported by close structural relationships with LTA₄hydrolase (LTA₄H ; EC 3.3.2.6). A structure-function analysis is necessary for the detailed understanding of the enzymatic mechanisms of Ap-B and to design inhibitors, which could be used to determine the complete <it>in vivo </it>functions of the enzyme.</p> <p>Results</p> <p>The rat Ap-B cDNA was expressed in <it>E. coli </it>and the purified recombinant enzyme was characterized. 18 mutants of the H³²⁵EXXHX₁₈E³⁴⁸Zn²⁺-binding motif were constructed and expressed. All mutations were found to abolish the aminopeptidase activity. A multiple alignment of 500 sequences of the M1 family of aminopeptidases was performed to identify 3 sub-families of exopeptidases and to build a structural model of Ap-B using the x-ray structure of LTA₄H as a template. Although the 3D structures of the two enzymes resemble each other, they differ in certain details. The role that a loop, delimiting the active center of Ap-B, plays in discriminating basic substrates, as well as the function of consensus motifs, such as RNP1 and Armadillo domain are discussed. Examination of electrostatic potentials and hydrophobic patches revealed important differences between Ap-B and LTA₄H and suggests that Ap-B is involved in protein-protein interactions.</p> <p>Conclusion</p> <p>Alignment of the primary structures of the M1 family members clearly demonstrates the existence of different sub-families and highlights crucial residues in the enzymatic activity of the whole family. <it>E. coli </it>recombinant enzyme and Ap-B structural model constitute powerful tools for investigating the importance and possible roles of these conserved residues in Ap-B, LTA₄H and M1 aminopeptidase catalytic sites and to gain new insight into their physiological functions. Analysis of Ap-B structural model indicates that several interactions between Ap-B and proteins can occur and suggests that endopeptidases might form a complex with Ap-B during hormone processing.</p

The distribution of cholecystokinin and vasoactive intestinal peptide in rhesus monkey brain as determined by radioimmunoassay

The concentration of cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in dissected cortical and subcortical areas of four rhesus monkeys' brains was determined by radioimmunoassay (RIA). Cerebral cortical samples from one human brain are included for comparison. Preliminary data from two baboon brains are described. The results are similar to previous studies on rat (1-7), human (7-12), porcine (12,13), bovine (3) and guinea pig brains (14) and indicate that: 1) both CCK and VIP are widely distributed in cortical and subcortical areas in these species, 2) CCK is generally more abundant than VIP in primate brain, and 3) the distribution of CCK and VIP in the rat brain parallel those in infrahuman primate and human brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25177/1/0000616.pd

College of Radiology, Academy of Medicine of Malaysia position on whole body screening CT scans in healthy asymptomatic individuals (2008)

To date, the College of Radiology (CoR) does not see any clear benefit in performing whole body screening computed tomography (CT) examinations in healthy asymptomatic individuals. There are radiation risk issues in CT and principles of screening should be adhered to. There may be a role for targeted cardiac screening CT that derives calcium score, especially for asymptomatic medium-risk individuals and CT colonography when used as part of a strategic programme for colorectal cancer screening in those 50 years and older. However, population based screening CT examinations may become appropriate when evidence emerges regarding a clear benefit for the patient outweighing the associated radiation risks