• The Korean Journal of Pharmacology
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• v.10 no.1 s.15
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• pp.47-52
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• 1974

The isolated rabbit gall bladder strips were prepared according to the technique described by Amer and Becvar (1969). The strips were placed in a bath containing 100 ml of Locke-Ringer solution maintained at $38^{\circ}C$. Oxygen was continuously bubbled through the solution. The tension of the muscle strip was initially adjusted to 0.7g. The contractile response was measured isometrically by a force-displacement transducer connected to a polygraph. The effect of a number of autonomic drugs were studied for their interaction with caerulein (Prof. V. Erspamer, F.I. 6934 Caerulein, Farmitalia, Italia), a gastrin or CCK.PZ like peptide, on isolated rabbit gall bladder strips. In this preparation caerulein produced contractions of CCK-PZ type, but the relative potency on a weight basis was 40 times that of CCK-PZ. The response of caerulein was not modified by either cholinergic or alpha or beta adrenergic blockade. However, the response of caerulein and of barium on the strips were prevented by papaverine or aminophylline. Isoproterenol, papaverine or aminophylline alone relaxed the preparation whereas caerulein, CCK-PZ, acetylcholine, serotonin, histamine or barium chloride contracted the preparation. In summary, it is concluded that caerulein on the gall bladder strip seems to act independently of the autonomic nervous system and mediated via mechanisms apparently similar to those involved in the action of barium chloride.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.500-512
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• 2010

Objectives : This study was designed to investigate the effects of SuJeom-san(SJS) extract in rats with caerulein-induced acute pancreatitis (AP). Methods : We examined changes of pancreatic weight, histological, immunohistochemical and gene expression of cyclooxygenase (COX-2). Thirty-six adult male Sprague-Dawley rats were divided into six groups as follow: normal(Nor), caerulein-induced (Con), caerulein + cefotaxime sodium(CT), caerulein + SJS 3 mg/kg(SJSA), caerulein + SJS 6 mg/kg(SJSB) and caerulein + SJS 12 mg/kg(SJSC) groups. Pancreatic tissues of rats from all groups were removed for histological observation and light, and electron microscopic examination. Platelet activating factor(PAF) and Interleukin-6(IL-6) levels were determined spectrophotometrically. Results : The ratio of pancreas/body weight was significantly(p<0.05) increased in the Con compared with Nor, but significantly(p<0.05) decreased in SJSA, SJSB, SJSC and CT groups compared with Con. Caerulein administration significantly increased(p<0.05) the levels of amylase, but SJSA, SJSB, SJSC and CT significantly(p<0.05) reduced the levels of these enzymes. The levels of platelet activating factor(PAF) increased in Con compared with Nor, but decreased in SJSA, SJSB, SJSC and CT groups compared with Con. Interleukin-6(IL-6) levels increased significantly in all groups compared to Nor at 6 hrs, but significantly(p<0.05) reduced in SJSA, SJSB, SJSC and CT groups compared with Con at 24 hrs. The levels of tumor necrosis factor(TNF)-${\alpha}$ levels increased in all groups compared to Nor at 6 hrs, but significantly(p<0.05) reduced in SJSA, SJSB, SJSC and CT groups compared with Con at 24 hrs. The COX-2 positive materials were observed in the pancreas of the Con, but these positive materials were decreased in the SJS extract treatment group. Conclusion : SJS is potentially capable of limiting pancreatic damage during AP by restoring the fine structure of acinar cells and tissue; therefore, we conclude that SJS may have beneficial effects in the treatment of caerulein-induced AP.

• The Korean Journal of Pharmacology
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• v.12 no.2 s.20
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• pp.7-11
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• 1976

A portion of duodenum laid pancreatic duct opening were perfused continuously with physiological saline under urethane anesthesia in rats. The pancreatic amylase secretory response to caerulein was studied with autonomic blockers, such as phenoxybenzamine, dibenamine, phentolamine, hexamethonium, propranolol, atropine, and cyproheptadine. The pancreatic amylase output to caerulein, 7.5ng/kg i.v., was markedly increased and the value was approximately three times greater than control. The caerulein-stimulated pancreatic amylase secretion was significantly decreased by i.v. phenoxybenzamine and propranolol treatment, but not by phentolamine or dibenamine. Secretory response of pancreatic amylase to caerulein was not affected by i.v. atropine, hexamethonium or cyproheptadine. These result lead to the conclusion that phenoxybenzamine may inherently inhibit the secretory response of pancreatic amylase to caerulein, and this effect was not related with ${\alpha}-adrenergic$ receptor blocking action.

• The Korean Journal of Pharmacology
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• v.12 no.2 s.20
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• pp.1-6
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• 1976

The effects of phenoxybenzamine and other related drugs were studied for their interaction with caerulein on gallbladder contraction in anesthetized animals and isolated gallbladder strips. Cholecystostomy and cystic duct ligation were made on anesthetized dog, cat and pig. Pressure changes of gallbladder were measured by a physiological pressure transducer connected to polygraph recorder. Isolated rabbit gallbladder strips were placed in a muscle chamber containing Locke-Ringer solution maintained at $38^{\circ}C$. The contractile responses were measured by a force-displacement transducer connected to polygraph recorder. Caerulein ($30{\sim}200$ ng/kg i.v.) produced marked contraction of gallbladder in situ and the cholecystokinetic potencies appear in decreasing order; dog, cat and pig. The response of caerulein was abolished by the large doses of phenoxybenzamine (15 mg/kg i.v.) but not affected with dibenamine, phentolamine or tolazoline. Cholecystokinetic effect of methacholine or barium chloride was also partially inhibited by phenoxybenzamine and the effect of caerulein was weakly inhibited intravenous injection of cyclophosphamide or papaverine. In isolated rabbit gallbladder strips, the response of contraction to caerulein were progressively inhibited by pretreatment of phenoxybenzamine along with time exposed. These results lead to the conclusion that phenoxytenzamine may inherently inhibit the contractile response of gallbladder to caerulein, and this effect was not related with ${\alpha}-adrenergic$ receptor blocking action.

• The Journal of Internal Korean Medicine
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• v.34 no.3
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• pp.298-311
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• 2013

Objectives : In this study, we aimed to investigate the effect of Eunhoebanchong-san (EBS) on caerulein-induced acute pancreatitis (AP) by detecting oxidative stress markers and performing histopathological examination. Methods : Thirty adult male Sprague-Dawley rats were divided into five groups as follows: normal (NOR), caerulein-induced (CON), caerulein+EBS (130 mg/kg, EA), caerulein+EBS (260 mg/kg, EB) and caerulein+EBS (520 mg/kg, EC) groups. Pancreatic tissues of rats from all groups were removed for apoptosis, and light, and electron microscopic examination. Blood of rats from all groups was obtained for oxidative stress markers and pathological examination. Pancreatic oxidative stress markers were evaluated by the measurements of serum amylase, and interleukin-6 (IL-6) levels were determined spectrophotometrically. Results : The ratio of pancreas/body weight increased significantly in the CON compared with the NOR, but decreased significantly in the EA, the EB, the EC groups compared with the CON. Caerulein administration resulted in a significant increase in amylase, but EBS reduced the levels of these enzymes. Interleukin-6 (IL-6) levels increased significantly in CON compared with NOR, but reduced in EA, EB, and EC group at 24 hrs. In the observations of optical microscopy and electron microscopy, the experimental groups showed significant decreases in pancreatic tissue inflammation, edema, vacuolization, necrosis compared to the control group. Altogether, this indicates EBS is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue. Conclusions : We concluded that EBS may have beneficial effects in the treatment of caerulein-induced AP.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.5
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• pp.644-649
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• 2013

In this study, we aimed to investigate the effect of GamiChungYi-tang(GCY-t) on caerulein-induced acute pancreatitis (AP). It is performed by detecting oxidative stress markers and observing histopathological examination. Thirty adult male rats(Sprague-Dawley) were divided into six groups as follows: normal (NOR,n=5), caerulein-induced (CON,n=5), caerulein+Cefotaxime Sodium(CT,n=5), caerulein+GCY-t (130 mg/kg, CHA,n=5), caerulein+GCY-t (260 mg/kg, CHB,n=5) and caerulein+GCY-t (520 mg/kg, CHC,n=5) groups. Pancreatic tissues of rats from all groups were removed for apoptosis and light, and electron microscopic examination. Blood of rats from all groups were collected for oxidative stress markers inspection and pathological examination. Pancreatic oxidative stress markers were evaluated by the measurements of leukocyte, serum amylase and platelet activating factor (PAF), Interleukin-6 (IL-6) levels were determined spectrophotometrically. CON group has a significant increase (p<0.05) in amylase compared with NOR, but CT and CHA, CHB, CHC groups reduced the levels of these enzyme. The levels of Platelet activating factor (PAF) were increased in CON compared with NOR, but decreased in CT and CHA, CHB, CHC groups compared with CON. Interleukin-6 (IL-6) levels were increased significantly in CON compared with NOR, but reduced in CT and CHA, CHB, CHC groups. In the observations of Optical microscopy and electron microscopy, The experimental groups showed the significant decreases in pancreatic tissue inflammation, edema, vacuolization, necrosis compared to the control group. After all, GCY-t is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue.

• The Korean Journal of Pharmacology
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• v.9 no.2
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• pp.17-27
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• 1973

Modifying the technique described by Schmidt, et al. (1972) the duodenum and stomach of female rats were perfused separately and contiunously with saline solution under urethane anesthesia. Secretory response of caerulein (Prof. V. Erspamer, F.I. 6934 Caerulein, Farmitalia, Italia), a gastrin or CCK-PZ like peptide, on acid, pepsin, bicarbonate and amylase were studied with and without simultaneous administration of secretin, CCK-PZ or other agents known secretory suppressives. A significant increase of acid, pepsin and amylase output was induced by intravenous infusion of caerulein. The response of acid secretion by caerulein in doses of 140 ng/100g/hr was equivalent to the response of histamine in the doses of $280\;{\mu}g/100g/hr$ and on a weight basis the potency of caerulein was approximately 2,000 times greater than histamine in rats. Acid secretory response of caerulein in the doses of 140 ng/100 g/hr was inhibited by simultaneous infusion of secretin in the doses of 0.2 u/ 100 g/hr, and the acid response was partly inhibited by concomitant infusion of histamine in the doses of $280\;{\mu}g/100g/hr$, but the response was enhanced by infusion of CCK-PZ in the doses of 0.2 u/100 g/hr. The secretory response of both aicd and enzymes were inhibited following administration of atropine in doses of 0.2 mg/100 g, but the response were not affected by hexamethonium in doses of 0.5 mg/100 g. In summary, it is concluded that caerolein is every effective in an increase of acid, pepsin and amylase secretion in rats through, possibly in part, the muscarinic and/or histaminic mechanism(s).

• Journal of Acupuncture Research
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• v.29 no.6
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• pp.35-45
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• 2012

Objectives : This study was designed to investigate Effects of Sujeom powder(SJP) pharmacopuncture Injected at Jung-wan($CV_{12}$) in rats with caerulein-induced acute pancreatitis(AP). Methods : We examined changes of organ weight, histology, immunohistochemistry and gene expression of cycolooxygenase 2(COX-2) in the pancreas. Twenty adult male Sprague-Dawley rats were divided into four groups as follow: normal(Nor), caerulein-induced(Con), caerulein+SJP pharmacopuncture 0.2mL injected at Jung-wan($CV_{12}$)(SA), and caerulein+SJP pharmacopuncture 0.8 mL injected at Jung-wan($CV_{12}$)(SB) groups. Pancreatic tissues of rats from all groups were removed for histological observation and light microscopic examination. Interleukin-6(IL-6) levels were determined spectrophotometrically. Results : The ratio of pancreas/body weights was significantly(p<0.05) increased in the Con, the SA and the SB compared with the Nor, but was slightly decreased in the SA and in the SB groups compared with the Con. Caerulein administration has significantly(p<0.05) increased in the levels of amylase, but the SA, the SB significantly(p<0.05) decreased in the levels of these enzyme. The levels of amylase were increased significantly with caerulein administration, but were inhibited significantly in the SA and in the SB groups. Interleukin-6(IL-6) levels were significantly(p<005) increased in all groups compared with the Nor, especially in the SB. were significantly increased. The levels of Tumor necrosis factor(TNF)-${\alpha}$ levels were significantly increased in all groups compared with the Nor. In the conclusion, the datum of IL-6 and TNF-${\alpha}$ are suggested that the inflamation was still existed actively at a point of measurement(24 hours later). The COX-2 positive materials are observed in the pancreas from the Con, but these positive materials are decreased in the SJP pharmacopuncture at Jung-wan($CV_{12}$) treatment group. Conclusion : SJP pharmacopuncture injected at Jung-wan($CV_{12}$) is potentially capable of limiting pancreatic damage during AP by restoring the fine structure of acinar cells and tissues. Therefore we can say that SJP pharmacopuncture Injected at Jung-wan($CV_{12}$) may have beneficial effects in the treatment of caerulein-induded AP. Further studies about the adequate amount of the SJP pharmacopuncture and about more effective route of administration is still required.

• The Korean Journal of Pharmacology
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• v.16 no.1 s.26
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• pp.35-39
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• 1980

In this study, the effects of phenoxybenzamine and related drugs on the action of CCK-PZ and caerulein were examined in isolated gall bladder of guinea pig and higher esophagus strip of fowl. The strips were placed in a bath containing Locke-Ringer solution maintained at $38^{\circ}C$. Oxygen was continuously bubbled through the solution. The contractile response was measured isometrically by a force displacement transducer connected to polygraph. In isolated gall bladder preparation caerulein produced contractile response of CCK-PZ type, but the relative potency on a weight basis was 30 times stronger than CCK-PZ. The response of caerulein or CCK-PZ was not blocked by cholinergic blocking agent and both alpha and beta adrenergic blockades, however, the response of caerulein or CCK-PZ was exceptionally blocked by phenoxybenzamine. In isolated esophagus strip CCK-PZ with high concentration produced marked contraction which was not modified by atropine and other blocking agents, whereas the response was blocked by phenoxybenzamine. These results lead to the conclusion that phenoxybenzamine inherently inhibits the contractile response of CCK-PZ and caerulein on esophagus and other smooth muscle.

• The Korean Journal of Pharmacology
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• v.11 no.1 s.17
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• pp.15-18
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• 1975

The effect of skin extracts of Korean amphibian, poisonous snake and fresh-water fish were determined for their caerulein-like action on rabbit gall bladder strips. The isolated gall bladder strips were prepared according to the technique described by Amer and Becvar(1969). The strips were placed in a bath containing 100ml of Locke-Ringer solution maintained at $38^{\circ}C$. Oxygen was continuously bubbled through the solution. The tension of the muscle strip was initially adjusted to 0.7g. The contractile response was measured isometrically by a force-displacement transducer connected to a polygraph. In this rabbit gall bladder strip caerulein produced contraction of CCK-PZ type. The skin extract of Korean amphibian also elicited similar contraction as caerulein, which extracted from Australian amphibian, Hyla caerulea, by Erspamer et al. The calculated amount was approximately $2{\mu}g$ caerulein per gram of skin tissue in Korean amphibian and the potency was about 1/200 of that seen in Australian amphibian. The contraction of gall bladder strip by our amphibians occurs in decreasing order; Rana Nigromaculata coreana Okada, Rana nigromaculata Hallowell, Hyla arborea japonica Gunther and Bombina orientalis Boulenger. The skin extracts of poisonous snake and fresh-water fish produced no caerulein-like activity.