Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the sulfated octapeptide of cholecystokinin (CCK8-S), the non-sulfated homolog (CCK8-NS) as well as the C-terminal di-, tri- and tetrapeptidic fragments (respectively CCK2, CCK3 and CCK4) were studied in vitro in rat hippocampal slices by extracellular recording of the spontaneous action potential discharge frequency of neurons located in the CA1 stratum pyramidalis. Bath-applied CCK8-S concentration-dependently increased the action potential discharge frequency of hippocampal CA1-neurons in concentrations ranging from 0.05 to above 1 microM. Both CCK8-NS and CCK4 exhibited reversible and concentration-dependent excitatory effects. They were 4 and 10 times less potent than CCK8-S, respectively, as concentrations of 2 microM CCK8-NS and 5 microM CCK4 were needed to evoke the same excitation as that induced for a given neuron by 0.5 microM CCK8-S. In contrast, none of the shorter fragments (CCK2 and CCK3) were effective in altering spontaneous discharge of CCK8-S-sensitive neurons even at concentrations of 100 microM. The pharmacologic profile of the excitatory response observed in the rat hippocampus follows the same pattern as the binding profile observed on brain membrane preparations. It is therefore concluded that the CCK receptors involved in this response seem to be related more to the 'central'- or B-type CCK receptors rather than to the 'peripheral'- or A-type CCK receptors.
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PMID:Excitatory effects of cholecystokinin in rat hippocampus: pharmacological response compatible with 'central'- or B-type CCK receptors. 325 90

The presence of high concentrations of both dopamine and cholecystokinin (CCK) in the striatum and in various limbic structures suggests that the CCK may not only influence dopaminergic transmission, but it also may be relevant to the psychopathology of schizophrenia and to the therapeutic effects of neuroleptics. By using a synaptosomal fraction isolated from the mouse cerebral cortex and [propionyl-3H]CCK8-sulphate ([3H]CCK8S) as a ligand, a single binding site for [3H]CCK8 with a KD value of 1.04 nM and a Bmax value of 42.9 fmol/mg protein was identified. The competitive inhibition of [3H]CCK8S binding by related peptides produced an order of potency of CCK8-sulphated (IC50 = 5.4 nM) greater than CCK8-unsulfated (IC50 = 40 nM) and greater than CCK4 (IC50 = 125 nM). The regional distribution of [3H]CCK8S binding in the mouse brain was highest in the olfactory bulb (34.3 +/- 5.6 fmol/mg protein) greater than cerebral cortex greater than cerebellum greater than olfactory tubercle greater than striatum greater than pons-medulla greater than mid brain greater than hippocampus greater than hypothalamus (12.4 +/- 2.1 fmol/mg protein). The repeated administration of haloperidol (2.5 mg/kg/tid) increased the binding of [3H]CCK8S in cerebral cortex from 31.8 +/- 1.7 to 38.9 +/- 5.2 fmol/mg protein. The varied distribution of CCK8S receptors may signify nonuniform functions for the octapeptide in the brain.
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PMID:Characterization of [3H]cholecystokinin octapeptide binding to mouse brain synaptosomes: effects of neuroleptics. 362 61

1 Mechanical activity was recorded in isolated muscle preparations from the circular and longitudinal layers of different regions of canine stomach (16 dogs). At least eight muscle strips were excised from each stomach: longitudinal (lo) and circular (ci) strips from fundus (Fu), corpus (Co) and antrum (An), and circular strips from the inner and outer portion of the pyloric ring. 2 Cholecystokinin 33 (CCK 33), cholecystokinin octapeptide (CCK 8), caerulein and pentagastrin produced the same pattern of responses, with differences in their potencies: caerulein was 10 times more potent than CCK 8, and CCK eight to ten times more potent than CCK 33 and pentagastrin. 3 The most characteristic effect of the CCK peptides was an increase in frequency of the phasic activity of Fu-ci, Co and An preparations (threshold 10(-10) mol/l for CCK 8), usually combined with weak or moderate increases of amplitude. 4 Slight tonic activations were observed in Fu-lo, Co-lo and An-lo (around 10% of the ACH maximum), and stronger tonic activations in Fu-ci and Co-ci (around 50% of the ACH maximum). 5 No responses to CCK were seen in pyrolic preparations. 6 Experiments with receptor antagonists (adrenoceptors, muscarinic and histamine receptors), and with tetrodotoxin indicate that the peptides act by a direct effect on smooth muscle.
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PMID:Contractile responses of canine gastric muscle to peptides of the cholecystokinin group. 365 82

Two major classes of immunoreactive cholecystokinin peptides (iCCK) have been identified in rat and pig brains: (i) large basic peptides (big iCCK) resembling the 33-amino acid porcine cholecystokinin (pCCK33) in size and charge; (ii) small acidic peptides (small iCCK) resembling the COOH-terminal fragments of CCK. Boiling 0.1 M HCl maximally extracts big iCCK; boiling 0.1 M NaOH maximally extracts small iCCK. The differences in hormonal forms removed by these extractants are not likely to be due to enzymatic conversion during the extraction procedures. Fractionation on Sephadex G-50 and starch gel electrophoresis combined with radioimmunoassay using three antisera of different specificities--(i) directed towards the NH2 terminus of pCCK33, (ii) produced by immunization with COOH-terminal fragment CCK8, (iii) produced by immunization with COOH-terminal fragment CCK4--are consistent with the hypothesis that a major fraction of big iCCK may represent intact cholecystokinin with a COOH-terminal extension, as has recently been suggested for gastrin, a molecule having a COOH-terminal pentapeptide identical with that of cholecystokinin.
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PMID:Extraction and immunochemical characterization of cholecystokinin-like peptides from pig and rat brain. 616 93

Two major classes of immunoreactive cholecystokinin peptides (iCCK) have been identified in rat and pig brains: (1) large basic peptides (Big iCCK) resembling pCCK33 in size and charge; (2) small acidic peptides (Small iCCK) resembling the COOH-terminal fragments of CCK. Boiling 0.1 N HCl maximally extracts Big iCCK; boiling 0.1 N NaOH maximally extracts Small iCCK. The differences in hormonal forms removed by these extractions are not likely to be due to enzymatic conversion during the extraction procedures. Fractionation on Sephadex G50 and starch gel electrophoresis combined with radioimmunoassay using 3 antisera of different specificities: (1) directed towards the NH2-terminus of pCCK33; (2) produced by immunization with CCK8; (3) produced by immunization with CCK4; are consistent with the hypothesis that a major fraction of Big iCCK may represent intact CCK with a COOH-terminus extension as has recently been suggested for gastrin, a molecule having a COOH-terminal pentapeptide identical with that of CCK.
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PMID:Nature of immunoreactive CCK in rat and pig brain. 617 97

The characteristics of cholecystokinin (CCK) binding to its receptors in a particulate membrane fraction of mouse cerebral cortex were studied by employing biologically active radioiodinated CCK prepared by conjugation with 125I-Bolton-Hunter (125I-BH) reagent. At 24 degrees C binding was rapid, reversible, and linearly related to protein content. Binding was maximal at acidic pH (6.5) and reduced by the presence of monovalent cations. Under physiological conditions (pH 7.4, 118 mM-NaCL, 4.7 mM-KCl) Scatchard plots of CCK binding were linear with a KD value of 1.27 nM and binding capacity of 115 fmol/mg protein. Optimal binding required the presence of both Mg2+ and EGTA, and was inhibited by the addition of micromolar concentrations of Cu2+ (ID50 = 30 microM). The cortical receptor recognized all major forms of CCK, with an order of potency of: cholecystokinin octapeptide (CCK8) greater than CCK greater than cholecystokinin tetrapeptide (CCK4). Desulfated cholecystokinin octapeptide (dCCK8) had a 10-fold lower affinity than CCK8. Dibutyryl cyclic GMP, a potent competitive inhibitor of CCK binding to receptors in pancreas, was not a specific inhibitor of CCK binding to brain receptors. These present results support the concept that CCK may function as a regulatory peptide in brain, and that the cortical CCK receptor is different from the receptors mediating the peripheral action of CCK.
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PMID:Characterization of receptors for cholecystokinin and related peptides in mouse cerebral cortex. 626 5

The cholecystokinin (CCK) receptor in purified plasma membranes prepared from mouse pancreatic acini had a binding affinity of 1.8 nM, an acid pH optimum between 6.0 and 6.5, and an analog specificity of CCK8 greater than CCK33 greater than desulphated CCK8 greater than CCK4. Binding of CCK to its receptor was abolished by pretreatment of plasma membranes with trypsin. When [125I]CCK was cross-linked to its receptors with disuccinimidyl suberate, and the preparation solubilized and subjected to gel electrophoresis and autoradiography, the hormone was associated with Mr 80 000 protein in both the presence and absence of the reducing agent dithiothreitol.
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PMID:The CCK receptor on pancreatic plasma membranes: binding characteristics and covalent cross-linking. 629 90

Prior studies have shown that the cerebral cortex cholecystokinin (CCK) receptor can bind CCK and gastrin analogs with high affinity. In the present work the brain CCK receptor had approximately a three times greater affinity for CCK8 than its C-terminal tetrapeptide (CCK4) while the C-terminal tripeptide (CCK3) was 1000-fold less potent than CCK4. Thus the C-terminal tetrapeptide appears to be the minimal C-terminal CCK sequence required for high affinity binding. Since brain membranes degrade various peptides including CCK, we also evaluated the stability of CCK analogs under the conditions used to measure receptor binding by the following three methods: (1) Studies of degradation-resistant analogs in binding assays; (2) analysis of analog degradation by high performance liquid chromatography (HPLC); and (3) determination of the change in potency of CCK analogs in competitive binding studies subsequent to preincubation with brain membranes. These studies indicated that degradation of analogs by the brain membranes although significant did not account for the differences in potency of analogs in competitive binding studies. Therefore, the observed differences in potencies of the analogs tested are due to the receptor affinity and not sensitivity of the analog to degradation.
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PMID:Binding specificity of the mouse cerebral cortex receptor for small cholecystokinin peptides. 632 3

Two radioimmunoassays specific for cholecystokinin-like immunoreactivity (CCK-LI) in human tissue are described. The first assay employed an antiserum (Z-69) directed to the sulphated tyrosine at the C-terminal end of CCK-33 and measured all biologically active molecular forms of CCK except the controversial C-terminal tetrapeptide amide (CCK4). The sensitivity of this assay was 0.6 pmol/g. A second assay (employing antiserum Z-91) measured CCK-LI forms larger than the octapeptide and had a sensitivity of 0.2 pmol/g. Both assays were characterised with endogenous human peptides. Acid (pH 2.5) and neutral extracts (pH 6.5) of human intestine and brain were assessed for CCK-LI concentrations and gel chromatography performed in the presence of 6 mol/l urea to elucidate the various molecular forms. Human cerebral cortex CCK-LI was almost all sulphated CCK-8, but large molecular mass forms were present, particularly in acid extracts, forming about 10% of the whole. Human duodenum and jejunum contained approximately equal amounts of large CCK, CCK 33/39 and of CCK-8. Both intestine and brain possess not yet isolated sulphated molecular forms which eluted between the pure CCK-8 and CCK-33/39 standards. The results obtained from this study indicate that the biosynthesis of CCK in human brain and gut is quantitatively different.
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PMID:Measurement and characterisation of human cholecystokinin-like immunoreactivity (CCK-LI) in tissues by radioimmunoassay. 652 56

A precise and specific radioimmunoassay method for measuring plasma cholecystokinin (CCK) is described. The present assay system using a stable tracer iodinated by means of a modified Chloramine-T method followed by purification on a Sephadex G-15 and a SP Sephadex C-25 column, as well as careful corrections for non-specific plasma effects, allows measurements of fasting plasma CCK in the low pmol/l range; the significant rise in plasma CCK following duodenal infusion of fat; and the significant diurnal variation of plasma CCK. Apparent immunoreactive meal-stimulated plasma CCK was eluted from a Sephadex G-50 superfine column in four fractions. The first and largest peak probably represents plasma CCK bound to plasma proteins and non-specific plasma effects, the second and smaller peak big CCK with molecular weight between some 5,000 and some 30,000, the shoulders following the second peak ordinary CCK33 and CCK39 variant, and the final, and by far the smallest peak, may possibly represent COOH-terminal tetra- (CCK4) or octapeptides (CCK8) of CCK.
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PMID:Radioimmunoassay of plasma cholecystokinin (CCK), duodenal release of CCK, diurnal variation of plasma CCK, and immunoreactive plasma CCK components in man. 719 31


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