OBJECTIVETo explore the regulatory effect of clearing-Heat secreting-bile regulating-Qi flow and activating blood circulation (CSRA) principle on cholecystokinin receptor (CCK-R) and its mechanism.

METHODSCholecystokinin (CCK) in serum of portal venous blood, maximum binding capacity (Bmax) and affinity (Kd) of CCK-R levels in gallbladder of guinea pigs allocated in four groups (control, high cholesterol, natural recovery and treated groups) were determined using radioimmunoassay and radioligand receptor assay (RRA). At the same time, changes of fasting volume (FV) and postprandial volume (PV) of gallbladder, fasting and postprandial bile (FB and PB) in gallbladder, gallbladder contraction rate (GCR) and cholesterol concentration (CC) in bile were observed.

RESULTSCompared with the control group, after two weeks of high cholesterol feeding, increase of FV, FB, PV, PB and CC (P < 0.05), and decrease of GCR (P < 0.01) and Bmax were found in cholesterol group, but with no significant change in Kd and CCK level. The above-mentioned criteria were restored to normal range in the treated group.

CONCLUSIONCSRA principle could promote the recovery of gallbladder contraction by regulating CCK-R expression in it, its mechanism is possibly correlated with reduction of cholesterol concentration in bile.

Animals ; Bile ; metabolism ; Cholecystokinin ; metabolism ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gallbladder ; physiopathology ; Guinea Pigs ; Hypercholesterolemia ; metabolism ; Male ; Medicine, Chinese Traditional ; Random Allocation ; Receptors, Cholecystokinin ; metabolism

To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acina response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.
Amylases/secretion ; Animal ; Benzodiazepinones/pharmacology ; Cells, Cultured ; Cholecystokinin/*pharmacology ; Devazepide ; Dose-Response Relationship, Drug ; Hormone Antagonists/pharmacology ; Lipase/secretion ; Male ; Pancreas/cytology/*drug effects/*secretion ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholecystokinin/antagonists & inhibitors ; Support, Non-U.S. Gov't

Pancreatic polypeptie (PP) is released from the pancreas in response to vagal stimulation. Amongst other effects, PP has been reported to inhibit pancreatic exocrine function. Apart from any potential physiological role, such inhibition could have important consequences for in vitro studies of pancreatic function employing acetylcholine as a stimulus. We have therefore tested the effect of bovine PP on two in vitro pancreatic preparations: the incubated, uncinate pancreas of young rats and the perfused cat pancreas. In the former, PP (10(-10)-10(-8)M) had little or no effect on enzyme discharge or45Ca efflux under basal conditions or during stimulation with caerulein, CCK-PZ or acetylcholine. In the perfused cat pancreas, similar concentrations of PP were also without effect on fluid secretion evoked by secretin infusion, or enzyme discharge evoked by CCK-PZ injection or infusion. We conclude that bovine PP has no direct effects on the cellular mechanisms responsible for pancreatic electrolyte secretion or enzyme discharge in the species studied.
Acetylcholine/pharmacology ; Amylases/secretion* ; Animal ; Caerulein/pharmacology ; Calcium/metabolism* ; Cats ; Cholecystokinin/pharmacology ; Electrolytes/secretion* ; In Vitro ; Pancreas/drug effects ; Pancreas/metabolism* ; Pancreatic Polypeptide/pharmacology* ; Perfusion ; Rats ; Secretin/pharmacology

Women often complain gut symptoms during pregnancy and the luteal phase of the menstrual cycle. To investigate the relationship between ovarian steroids and the abnormal gut motility and sensitivity, the expressions of cholecystokinin (CCK), calcitonin gene-related peptide (CGRP) and their receptors in stomach were studied in ovariectomized rats. Blood samples were collected for estradiol (E(2)), progesterone (P(4)), CCK and CGRP radioimmunoassay. Expression of CCK(A) receptor in fundus was assessed by Western blot and CGRP receptor was determined by (125)I-CGRP radioligand binding assay (RBA). The replacement therapy with estradiol benzoate (EB) could dose-dependently increase the plasma CCK level and the expression of gastric CCK(A) receptor (P<0.05 respectively). P(4) replacement therapy could stimulate the release of CGRP and increase the binding sites of CGRP receptors in stomach (P<0.05 respectively). The combined effect of EB and P(4) was to stimulate the release of CCK and CGRP, and to increase the expressions of gastric CCK(A) and CGRP receptors. These results indicate that EB could inhibit gastric emptying by increasing CCK secretion and CCK(A) receptor expression in ovariectomized rats. P(4) could increase gut sensitivity by up-regulating the release of CGRP and the activity of CGRP receptor. It could be deduced from these observations that CCK(A) and CGRP receptor antagonists could be used for female patients who suffer from gastrointestinal dysfunction closely related with the menstrual cycle, such as distension, satiety, bloating and abdominal pain.
Animals ; Calcitonin Gene-Related Peptide ; blood ; Cholecystokinin ; blood ; Estradiol ; analogs & derivatives ; pharmacology ; physiology ; Female ; Gastric Emptying ; drug effects ; physiology ; Ovariectomy ; Progesterone ; pharmacology ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitonin Gene-Related Peptide ; metabolism ; Receptors, Cholecystokinin ; metabolism ; Stomach ; metabolism ; physiology

OBJECTIVETo investigate the relationship between the effects of zinc on hippocampal cholecystokinin (CCK) positive neurons and learning and memory ability of lead-exposed rats.

METHODSThirty-six Wistar rats were divided into control group, lead-exposed group (drunk 6.15 mmol/L of lead solution) and lead-zinc group (drunk 6.15 mmol/L of lead + 3.10 mmol/L of ZnSO(4) solution) randomly. Y-maze test was used to study learning and memory ability in rats; Atomic absorption method was used to determine serum and hippocampal lead content; ABC immunohistochemistry and quantitative graphic analysis were used to investigate the changes of CCK positive neurons in different hippocampal subfields in lead-exposed rats.

RESULTSThe learning and memory ability in lead-exposed rats were significantly lower (P < 0.05) while the serum and hippocampal lead content in lead-exposed rat were significantly higher (P < 0.05) than those in control and lead-zinc group. The number and optical density of CCK positive neurons in CA(1) and CA(3) areas of lead-exposed rats were significantly lower (P < 0.05) than those in control and lead-zinc group. No differences in these indexes between the control and lead-zinc group were found (P > 0.05).

CONCLUSIONLead may damage the learning and memory ability and affect the number of CCK positive neurons in lead-exposed rats. Zinc might play an important role in preventing lead-induced damages.

Animals ; Cholecystokinin ; metabolism ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Zinc ; pharmacology

OBJECTIVETo investigate the expression of gastrin in human gastric cancer cell line SGC-7901 and the effects of gastrin-17 and anti-gastrin mAb on its growth.

METHODSThe expression of gastrin was determined by immunohistochemistry with anti-gastrin mAb prepared by our group. In a series of experiments, the growth of SGC-7901 cells was evaluated by MTT assay on cells grown in serum-free medium and treated with gastrin-17 and/or anti-gastrin mAb.

RESULTSImmunohistochemical examination of SGC-7901 cells revealed a specific gastrin immunoreactivity. Gastrin-17 significantly stimulated cell growth at the concentrations of 1 x 10(-9) mol/L approximately 1 x 10(-5) mol/L in a dose-dependent manner. The growth of SGC-7901 cells treated with anti-gastrin mAb, either alone or in combination with gastrin-17 (1 x 10(-7) mol/L), was significantly inhibited.

CONCLUSIONGrowth of human gastric cancer cells SGC-7901 can be stimulated in an autocrine fashion. The gastrin-stimulated growth of gastric cancer cells can be blocked by anti-gastrin mAb bound specifically with gastrin. Further study on the significance of anti-gastrin mAb in designing immunotherapy targeting to gastrin or gastrin receptor is warranted.

Antibodies, Monoclonal ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Gastrins ; biosynthesis ; genetics ; immunology ; Humans ; Receptor, Cholecystokinin B ; biosynthesis ; genetics ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo observe the effect of Fructus Aurantii Immaturus (FAI) on the electro-activity of small intestines in rats, and evaluate the interrelations between the FAI regulating effect and choecystokinin (CCK) and somatostatin (SS).

METHODSMigrating myoelectric complex (MMC) cyclic period, the ratio of the active time to the cyclic period, and the number of the fast wave within the active time per minute were observed between FAI and the normal saline group by external alimentary canal electrodes; the CCK contents in dorsomedial hypothalamic nucleus (DMH), ventromedia hypothalamic nucleus (VMH), lateral hypothalamus area (LHA) and SS in VMH, LHA, paraventricular nucleus (PVN) by using immuno-chemistry technique and micro-image pattern quantitative analysis and scanning system.

RESULTSThe MMC cyclic period shortened, the ratio of the active time to the cyclic period increased and the number of the fast wave within the active time per minute increased in the FAI group, which showed significant difference from the normal saline group; CCK positive neurons were reduced in the areas of DMH, VMH and LHA, SS positive neurons were increased in the areas of VMH, LHA and PVN in the FAI gioup,which showed significant difference compared with the normal saline and the blank control group.

CONCLUSIONFAI can stimulate the electro-reactivity of small intestines. The stimulative effect of FAI might be related to CCK and SS in hypothamus.

Animals ; Central Nervous System Stimulants ; pharmacology ; Cholecystokinin ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hypothalamus ; drug effects ; metabolism ; Intestine, Small ; drug effects ; physiology ; Myoelectric Complex, Migrating ; drug effects ; Rats ; Somatostatin ; metabolism

Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.
Amylases/metabolism ; Animal ; Baclofen/pharmacology ; Baclofen/analogs & derivatives* ; Bicuculline/pharmacology ; Cholecystokinin/metabolism ; Dose-Response Relationship, Drug ; Electric Stimulation ; GABA/pharmacology* ; GABA Antagonists/pharmacology ; Gastrin-Releasing Peptide/metabolism ; Hormones/pharmacology ; In Vitro ; Pancreas/secretion* ; Pancreas/enzymology ; Pancreas/drug effects* ; Rats ; Receptors, GABA-A/metabolism ; Secretin/metabolism ; Somatostatin/pharmacology ; Tetrodotoxin/pharmacology

The aim of this study was to explore the effects of cholecystokinin octapeptide (CCK-8) on cardiac function and the receptor mechanism in anesthetized rats. The mean arterial pressure (MAP), heart rate (HR), the left ventricle systolic pressure (LVP) and the maximal/minimum rate of LVP (+/-LV dp/dt(max)) were measured. The results obtained are as follows. (1) Low dose of CCK-8 (0. 4 microgram/kg i.v.) caused tachycardia and slight increase in MAP, LVP and LV dp/dt(max) (P<0.01), while medium dose (4.0 microgram/kg i.v.) and high dose of CCK-8 (40 microgram/kg i.v.) elicited a bradycardia and marked increase in MAP, LVP and LV dp/dtmax (P<0.01). (2) Proglumide (1.0 mg/kg i.v.), a CCK-receptor (CCK-R) antagonist, significantly inhibited the pressor effects of CCK-8, whilst it reversed the bradycardic responses (P<0.01). (3) Using reverse transcription polymerase chain reaction (RT-PCR), CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR) mRNA were expressed in myocardium of rats. The above results indicate that CCK-8 may enhance cardiac function in a dose-dependent manner and elicit a change in HR, which is likely induced by the activation of CCK-R on myocardium.
Animals ; Dose-Response Relationship, Drug ; Heart Rate ; drug effects ; Male ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholecystokinin ; drug effects ; Sincalide ; administration & dosage ; pharmacology ; Ventricular Function, Left ; drug effects ; Ventricular Pressure ; drug effects

OBJECTIVETo investigate the effect of lithium on hippocampal cholecystokinin (CCK) and neuronal nitric oxide synthase (nNOS) positive neurons and its relationship to the learning and memory ability of lead exposed rats.

METHODSWistar rats were randomly divided into the control group, the lead group, four lead + LiCl (3, 30, 300, 3,000 mg/kg) groups. Four lead + LiCl groups were fed with food containing 3, 30, 300, 3,000 mg/kg LiCl respectively. The lead + LiCl groups and the lead group were administered with distilled water containing 0.2% PbAc. The body weight was measured and the difference of body development was observed. Y-maze test was used for studying the effects of lead on the learning and the memory ability in rats. ABC immunohistochemistry was used for investigating the changes of CCK positive neurons in hippocampus of lead-exposed rats.

RESULTSCompared with the control group and the lead + LiCl groups, the learning and memory ability of lead exposed rats was significantly higher (P < 0.05). The number of CCK positive neurons in hippocampus lead exposed rats fed with lithium (3, 30, 300 mg/kg) was significantly higher than that in the lead exposed rats (P < 0.05).

CONCLUSIONThe lead may damage the learning-memory ability of the rats. It might be related to the changes of CCK positive neurons in hippocampus in lead exposed rats. The lithium of the low dose might play an important role in preventing lead-induced damages.

Animals ; Cholecystokinin ; metabolism ; Dose-Response Relationship, Drug ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Lead ; toxicity ; Lithium ; pharmacology ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurons ; enzymology ; Nitric Oxide Synthase ; metabolism ; Random Allocation ; Rats ; Rats, Wistar