Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholecystokinin (CCK) binding sites were localized by in vitro autoradiography in human postmortem brain materials from 12 patients without reported neurological diseases using [125I]Bolton-Hunter CCK octapeptide (BHCCK-8) as a ligand. The pharmacological characteristics of BHCCK-8 binding to mounted tissue sections were comparable to those previously reported in the rat. CCK-8 being the most potent displacer, followed by caerulein, CCK-4, and gastrin I. The distribution of BHCCK-8 binding sites was heterogeneous. These sites were highly concentrated in a limited number of gray matter areas and nuclei. The highest binding densities were seen in the glomerular and external plexiform layers of the olfactory bulb. BHCCK-8 binding sites were also enriched in the neocortex, where they presented a laminar distribution with low levels in lamina I, moderate concentration in laminae II to IV, high density in lamina V, and low levels in lamina VI. A different laminar distribution was seen in the visual cortex, where a low receptor density was observed in lamina IV but higher density in laminae II and VI. In the basal ganglia the nucleus accumbens, caudatus, and the putamen presented moderate to high densities of binding sites, while the globus pallidus lacked sites of BHCCK-8 binding. In the limbic system the only area presenting moderate to high density was the amygdaloid complex, particularly in the granular nucleus, while most of the thalamic nuclei were extremely poor or lacked BHCCK-8 binding. The hippocampal formation showed low (CA1-3) to moderate (subiculum) densities. Midbrain areas generally disclosed very low levels of BHCCK-8 binding sites. The pontine gray and the nucleus reticularis tegmenti pontis showed a relatively high density of CCK-8 receptor specific binding. Moderate to very high densities were found in few nuclei of the lower brainstem and spinal cord as the inferior olives and their accessory nuclei, the arcuate nuclei, the striae medullares, the efferent (motor) nucleus of the vagus, and the substantia gelatinosa of the cervical and thoracic spinal cord. These results are discussed in relation to the distribution of endogenous peptide and to the known physiological and pharmacological effects of substances acting on these receptors.
 ...
PMID:On the distribution of cholecystokinin receptor binding sites in the human brain: an autoradiographic study. 350 67

Cholecystokinin (CCK) is a heterogeneous gut hormone which is also synthetized in extra-intestinal endocrine cells and neurons. In order to examine the possibility that CCK peptides are local modulators of calcitonin secretion, we have studied the structure-activity relationship on calcitonin secretion from perfused canine thyroid lobes as well as the presence and molecular nature of CCK in the thyroid. Peptides containing the intact COOH-terminal tetrapeptide amide of CCK (CCK-4, CCK-5, pentagastrin, CCK-8 and gastrin-17) all induced dose-dependent (0.1, 3 and 100 nmol/l) increases in calcitonin release (P less than 0.05, n = 4) with biphasic secretion during 6-min infusion periods. The deamidated tetrapeptide and the COOH-terminal tripeptide were without effect. Gel chromatography of neutral water and acid-ethanol extracts of thyroid tissue, monitored by sequence-specific CCK and gastrin radioimmunoassays, disclosed a variety of CCK and gastrin peptides of which a predominant form resembled small molecular forms like CCK-4 and CCK-5. The presence in the thyroid of small CCK-like peptides and the pronounced effect of such peptides on calcitonin secretion suggest that calcitonin secretion is modulated by local release of small CCK peptides. They could originate from intrathyroidal nerves or from sub-populations of C-cells.
 ...
PMID:Cholecystokinin peptides as local modulators of thyroidal calcitonin secretion in the dog? 366 49

Cholecystokinin octapeptide (CCK-8), administered intracerebroventricularly (i.c.v.), will suppress feeding. The aim of the present study was to determine the pharmacological characteristics of this satiety inducing effect in rats. For this purpose, we employed a feeding bioassay model in 24 h fasted rats and examined the effects of CCK-8 and a variety of structurally related analogs on latency to feed after i.c.v. injection and on the amount of food and water consumed as measured after the initiation of feeding in sequential 20-min epochs for 1 h. CCK-8, given in doses of 0.1, 1 and 10 nmol, produced a dose-dependent increase in feeding latency and a reduction of food intake during the first 20 min after initiation of feeding. Food intake during the next 40 min and water consumption were not altered. Plasma levels of CCK-like immunoreactivity after an i.c.v. injection of a dose of CCK-8 which blocked feeding (10 nmol) rose insignificantly from 117 to 125 pg/ml. In contrast, at the minimally effective dose of CCK-8 after i.v. administration (10 nmol), which also produced an inhibition of feeding, the plasma level was 1430 pg/ml. This difference indicates that plasma levels of CCK after i.c.v. CCK-8 are not adequate to produce the observed feeding suppression and suggests that the effects of i.c.v. CCK-8 are not mediated by a peripheral redistribution. Systematic dose response studies revealed the following rank order of potencies: CCK-8 greater than or equal to G-17 II much greater than CCK-8 NS = G-17 I greater than or equal to CCK-4 = CCK 26-29 = 0. Only gastrin-17 II (sulfated) produced an effect comparably significant to CCK-8. I.c.v. proglumide at 2500 nmol failed to modify the effects of CCK-8 at 10 nmol after i.c.v. injection. These data demonstrate that the structural requirements for feeding suppressive activity in rat brain are the carboxyterminus with a sulfated tyrosine residue, located 6 to 7 residues from the carboxyterminus, as present in CCK-8 and gastrin-17 II.
 ...
PMID:Intracerebroventricular injections of cholecystokinin octapeptide suppress feeding in rats--pharmacological characterization of this action. 374 26

Cholecystokinin (CCK) binding to its receptors on a muscularis membrane fraction of bovine gallbladder was characterized using a biologically active CCK-33-[125I]Bolton-Hunter conjugate. Receptor binding was localized to the muscularis layer of the gallbladder; no binding was seen on either mucosal or serosal membranes. At 24 degrees C and pH 6.5, binding was maximal after 60-90 min of incubation, remained at a plateau for at least 240 min, and was reversed by the addition of unlabeled CCK-8. Optimal binding was seen at pH of 5.5 and required the presence of magnesium. Gallbladder binding data, best fit by a two-parameter model using a nonlinear least-squares computer program, was consistent with a single order of binding sites with a Kd of 618 +/- 168 pM and a binding capacity of 100.5 +/- 15.7 fmol/mg prot (mean +/- SE, n = 5). CCK-8 and CCK-33 inhibited 125I-CCK binding to gallbladder membranes with similar potencies, whereas desulfated CCK-8, gastrin I and II, and CCK-4 were at least 500 times less potent than CCK-33. The CCK antagonists dibutyryl cGMP and proglumide inhibited 125I-CCK binding with an IC50 of 31 and 600 microM, respectively. The present studies therefore demonstrate the existence of a specific CCK receptor on bovine gallbladder muscularis membranes with a high degree of selectivity for CCK analogues.
 ...
PMID:Characterization of cholecystokinin receptors on bovine gallbladder membranes. 609 78

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.
 ...
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.
 ...
PMID:Nature of immunoreactive CCK in rat and pig brain. 617 97

Studies were performed to investigate the effects of neurotransmitters and neurotransmitter candidates (substance P, VIP, somatostatin, Met-enkephalin, gastrin-17, CCK-4 and -8, neurotensin and TRH) of the newly discovered peptidergic nervous system on lower oesophageal sphincter pressure in anaesthetized pigs. All neuropeptides were infused over 2 min periods in 6 different doses, separated by resting periods of at least 1 min, directly into the arterial supply of the lower oesophageal sphincter. Substance P caused a dose-dependent increase in lower oesophageal shpincter pressure; the threshold dose was 9 pmol . kg-1 . min-1 and half maximal response occurred at 72 pmol . kg-1 . min-1. None of the other polypeptides, however, influenced the resting lower oesophageal sphincter. These studies show that substance P is a potent stimulant of smooth muscle in the lower oesophageal sphincter, suggesting that this peptide may be an important regulator of lower oesophageal sphincter pressure.
 ...
PMID:Effects of regulatory peptides on the porcine lower oesophageal sphincter. 618 84

Previously, vasoactive intestinal polypeptide was localized to intrathyroidal nerve fibers. It stimulates iodothyronine secretion in mice. In the present study two populations of nerve fibers containing substance P and gastrin/cholecystokinin (CCK)-like immunoreactivity, respectively, were demonstrated in the thyroid gland of several mammals. The substance P fibers occurred around blood vessels and follicles, whereas the gastrin/CCK fibers occurred mainly around follicles. In the chicken thyroid and ultimobranchial glands only substance P-containing fibers could be demonstrated. Such fibers were particularly numerous in the ultimobranchial gland. CCK-4, CCK-8, and substance P did not increase thyronine secretion measured as release of radioiodine into the circulation of mice pretreated with Na125I and T4. The TSH-induced release of radioiodine was also unaffected. Calcitonin secretion in rats was stimulated by CCK-4, CCK-8, substance P, and vasoactive intestinal polypeptide.
 ...
PMID:Neuropeptides in the thyroid gland: distribution of substance P and gastrin/cholecystokinin and their effects on the secretion of iodothyronine and calcitonin. 619 Jun 43

Antibody specific for the amino-terminal region of cholecystokinin octapeptide (CCK-8) was generated in a highly reproducible way in New Zealand white rabbits by a novel immunization procedure which involves immunization with CCK-8 peptide conjugate coupled with keyhole limpet hemocyanin (KLH) and inhibiting cross-reacting antibody formation by treatment of the animals with a potent tolerogenic conjugate of beta-alanyl-tetragastrin and a copolymer of D-glutamic acid and D-lysine (D-GL). The antisera thus produced specifically react with an amino-terminal region of CCK-8 but not with the non-sulfate form of CCK-8, nor with the carboxy-terminal region which shares a cross-reactive determinant among gastrin and cholecystokinin-related peptides (caerulein, CCK-4, CCK-8, CCK-33 and CCK-39). The antisera produced by this method allowed us to measure specifically CCK in extracts from tissue such as duodenum containing gastrin and CCK at comparable levels.
 ...
PMID:Production of rabbit antibody specific for amino-terminal residues of cholecystokinin octapeptide (CCK-8) by selective suppression of cross-reactive antibody response. 630 Feb 48

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.
 ...
PMID:Binding specificity of the mouse cerebral cortex receptor for small cholecystokinin peptides. 632 3


<< Previous 1 2 3 4 5 6 Next >>