한국산 무당개구리 피부에 존재하는 Bombesin 유사면역 반응물질의 순수정제 및 생물학적 활성

권혁일(Kwon, Hyeok-Yil),김일(Kim, Yil),박형진(Park, Hyoung-Jin) 대한생리학회 1990 대한생리학회지 Vol.24 No.2

The present investigation was performed to purify bombesin-like immunoreactivity (BBS-LI) from the skin of frogs, B. orientalis inhabiting Korea. For extraction of BBS-LI, the fresh skin of 360 g from frogs was immersed in 1,800 ml of 100% methanol and then kept at 4℃ for 5 days. BBS-LI was partially purified by liquid chromatography using an alkaline alumina column followed by a Sephadex G-10 column. BBS-LI was further purified by using sequential HPLC of reversed phase C18 preparation, gel permeation, SP-ion exchange and reversed phase C18 analysis. BBS-LI in fractions of each step was monitored by radioimmunoassay for which bombesin antiserum with a titer of 1 : 188,800 was raised in a guinea pig. Eventually, two different BBS-LI were successfully purified and each BBS-LI showed the following character. 1) BBS-LI was well separated into two peaks in SP-ion exchange HPLC. One (BBS-LI-K1) bound to the column while the other (BBS-LI-K2) did not. 2) BBS-LI-K1, 73.8% of total BBS-LI, was not differentiated from synthetic bombesin in reversed phase C18 analytical and gel permeation HPLC. 3) BBS-LI-K2, 26.2% of total BBS-LI, eluted later than synthetic bombesin in reversed phase C18 analytical HPLC, but it eluted with a retention time identical to that of synthetic bombesin in gel permeation HPLC. 4) The two forms of BBS-LI and synthetic bombesin identically stimulated gastrin release and pancreatic exocrine secretion including volume, protein output and amylase output in anesthetized rats. It is concluded from the above results that the skin of B. orientalis contains two different forms of BBS-LI which are very identical to bombesin immunologically and biologically. In comparison with synthetic bombesin containing 14 amino acid residues, the major form shows quite similar pattern in all HPLC used in the present study, but the minor form exhibits quite different pattern in SP-ion exchange and reversed phase C18 analytical HPLG.

방사면역측정을 위한 항 Gastrin 혈청의 생산 및 평가

박형진,권혁일,이윤렬,신원임,서상원,오양석,Park, Hyoung-Jin,Kwon, Hyeok-Yil,Lee, Yun-Lyul,Shin, Won-Im,Suh, Sang-Won,Oh, Yang-Suk 대한생리학회 1989 대한생리학회지 Vol.23 No.1

New Zealand white 계의 토끼에게 EDC를 사용하여 hemocyanin에 접합시킨 human G-17-I을 면역한 결과 gastrin의 방사면역측정에 적합한 항 gastrin 혈청을 얻는데 성공하였다. 본 실험에서 얻은 항 gastrin 혈청의 역가는 1:25,000이며 human G-17-I과 human big gastrin에 매우 친화력이 높은 반면 다른 위장관 peptide 들과는 교차반응성이 아주 낮았다. 본 항 gastrin 혈청의 effective affinity constant는 $1.77{\times}10^{11}/M$이었다. 또한 총 결합부위(total binding sites)는 255 nM, 이질성지수(heterogeneity index)는 0.84 그리고 average affinity constant는 $0.79{\times}10^{11}/M$이었다. 본 실험에서 얻은 항 gastrin 혈청을 사용하여 사람과 흰쥐의 혈장 gastrin 농도를 방사면역측정법으로 측정한 결과 이미 잘 알려진 결과와 동일한 성적을 얻을 수 있었다. 이러한 결과들을 종합하여 볼때 본 실험에서 얻은 항 gastrin 혈청은 생리적농도로 존재하는 gastrin의 방사면역측정에 적합한 것으로 생각된다. In order to produce antibody for use in radioimmunoassay of gastrin in physiological concentration, four rabbits of New Zealand white were immunized with synthetic human gastrin-17-I conjugated to hemocyanin with EDC. Among them, only one rabbit produced antibody that could bind 50% of $^{125}I-gastrin$ at a final dilution of 1:25,000. $^{125}I-gastrin$ was prepared with synthetic human gastrin-17-I and $NaI^{125}$ by lactoperoxidase technique. The product was then purified on a column of Sephadex Gl5/G5O (7:3, w/w) followed by a column of DEAE sephadex A-25. The specific radioactivity of the purified $^{125}I-gastrin$ was in the range of 347-1429 ${\mu}Ci/nmole$ when determined by the self-displacement method. The effective affinity constant $(K_{eff})$, total binding sites (N), heterogeneity index $({\alpha})$ and average affinity constant $(K_{0})$ of the anti-gastrin serum calculated from Scatchard plot as well as Sips plot were $1.77{\times}10^{11}/M$, 255 nM, 0.84 and $0.79{\times}10^{11}/M$, respectively. When radioimmunoassay was performed with the anti-gastrin serum, it was confirmed that the mean concentration of gastrin immunoreactivity in plasma was increased by feeding in humans and rats, and also increased by bombesin administration in rats. The results indicate that the anti-gastrin serum produced in the present investigation is suitable for radioimmunological determination of gastrin in physiological concentration.

흰쥐에서 췌장의 외분비 기능에 미치는 adrenaline 동작성 신경계의 영향

신원임,김미령,권혁일,이윤렬,박형진,Shin, Won-Im,Kim, Mi-Ryoung,Kwon, Hyeok-Yil,Lee, Yun-Lyul,Park, Hyoung-Jin 대한생리학회 1986 대한생리학회지 Vol.20 No.2

The present study was performed to investigate a possible influence of the adrenergic nervous system on pancreatic exocrine secretion stimulated by intraduodenal acid perfusion. Pancreatic secretion was collected in rats anesthetized with urethane after 24 hours fasting. The duodenal lumen was perfused (0.2 ml/min) with HCI solution in a concentration of 0.005, 0.01, 0.02, 0.05 or 0.1 N When the volume of panceratic juice secreted for IS min became constant phentolamine (1 mg/kg), $noradrenaline\;(10\;{\mu}g/kg),\;Propranolol\;(1\;mg/kg),\;and \;isoproterenol\;(1\;{\mu}g/kg)$ were administered through the jugular vein in bolus. The secretory volume and protein output were measured in the pancreatic juice collected for 15 min. 1) HCI, perfused intraduodenally in graded concentrations from 0.005 N to 0.1 N, increased the pancreatic secretory volume and protein output dose-dependently. 2) In the basal state as well as in the stimulated state by the duodenal acid perfusion, phentolamine increased the pancreatic secretory volume and protein output while propranolol inhibited the volume and protein output. 3) In the basal state, noradrenaline did not change the pancreatic secretory volume but increased the protein output while isoproterenol increased both of the secretory volume and the protein output. These results strongly suggest that ${\alpha}-adrenoceptors$ in the rat pancreas exert an inhibitory influence on the pancreatic exocrine secretion including volume and protein output in the basal state as well as in the stimulated state by the intraduodenal acid perfusion while ${\beta}-adrenoceptors$ play a stimulatory role in the pancreatic exocrine secretion. However, in the physiological situation, adrenergic excitation may stimulate the protein output through ${\beta}-adrenoceptors$ without change in the secretory volume in the rat pancreas.

Isolation of Bombesin-Like Substances from the Skin of the Frog, Bombina orientalis: Its Molecular Heterogeneity and Biological Activity

박형진,이윤열,권혁일,신원임,서상원,Park, Hyoung-Jin,Lee, Yun-Lyul,Kwon, Hyeok-Yil,Shin, Won-Im,Suh, Sang-Won The Korean Physiological Society 1989 대한생리학회지 Vol.23 No.1

Bombesin (BBS)은 유럽에 서식하는 무당개구리(Bombina bombina)의 피부로 부터 발견되었으며 이것은 14개의 amino acid로 구성되어 있음이 잘 알려져 있다. 한국에도 유럽의 무당개구리와 종(species)이 다른 무당개구리인 Bombina orientalis가 서식함이 알려졌으나 이 무당개구리의 피부에 BBS가 존재하는 지는 확실치 않다. 그러므로 본 실험에서는 한국에 서식하는 무당개구리의 피부로부터 BBS 유사물질(BBS-LS)을 추출하여 분자적 이질성과 생물학적 활성을 측정하고자 하였다. 박리한 무당개구리 피부를 100% methanol로 처리하여 얻은 추출물의 일부를 Sephadex G-50, superfine column에 부하하고 여기에서 얻은 chromatogram을 분석한 결과 BBS-LS의 3.5%는 합성 gastrin releasing peptide (GRP-27) 보다 앞에 용출되었으며 나머지 96.5%는 GRP-27과 합성 BBS-14의 사이에 용출되었다. alkaline alumina column과 Sephadex G-10, fine column 그리고 Sephadex G-50, superfine column을 연속적으로 이용하여 methanol 추출물로 부터 BBS-LS를 정제 하였다. 정제된 BBS-LS를 Sephadex G-50, superfine column으로 분석한 결과 합성 GRP-27과 합성 BBS-14 사이에 용출되어 BBS-LS가 이미 알려진 BBS-14와 분자의 크기에 있어서 다른 물질임을 알 수 있었다. 정제된 BBS-LS를 reversed phase HPLC로 분석한 실험은 이러한 결과를 더욱 확실히 뒷받침하였다. 정제된 BBS-LS를 합성 BBS-14와 비교하여 생물학적 활성을 검토한 결과 흰쥐에서 gastrin의 분비, 췌장액의 분비, 회장의 수축을 촉진하고 guinea pig 담낭의 수축을 증가시키는 등 이들 두물질이 매우 유사한 생물학적 활성을 지니고 있음을 발견하였다. 이러한 결과로 보아 한국에 서식하는 무당개구리의 피부는 서로 다른 두가지 형태의 BBS-LS를 함유하고 있으며 그 중에서 96.5%를 차지하는 BBS-LS는 합성 BBS-14와 분자적 이질성을 지니나 유사한 생물학적 활성을 지니고 있음을 알 수 있었다. Molecular property as well as biological activities of bombesin-like substance (BBS-LS) isolated from the skin of B. orientalis in Korea was compared with those of synthetic BBS-14. BBS-LS in the crude extract was applied on a Sephadex G-50, superfine column $(1.6{\times}112\;cm)$. On chromatogram, the first peak (3.5% of BBS-LS) was found ahead of synthetic GRP-27, and the second peak (rest) between synthetic GRP-27 and synthetic BBS-14. The main form of BBS-LS was successfully purified by using a column of alkaline alumina followed by sequential gel-filtrations on a column of Sephadex G-10, fine and a column of Sephadex G-50, superfine. Chromatographic analysis of the purified BBS-LS using a column of Sephadex G-50, superfine and reversed phase HPLC revealed that the main form of BBS-LS in the skin of B. orientalis could be distinctly different from either BBS-14 or GRP-27 in molecular size. The purified BBS-LS exerted biological activities quite identical to those of synthetic BBS-14. The results of the present investigation indicate that the skin of B. orientalis contains BBS-LS composed of two distinct forms. The main form of BBS-LS purified in the present study is heterogenous to both synthetic BBS-14 and GRP-27 in molecular size but identical to BBS in biological activities.

강원도 지역에 서식하는 무당개구리에서 생물학적 활성을 지닌 Bombesin 유사 Peptide 에 관한 연구

박형진,이윤렬,권혁일,김일,유일재,D . R . Marshak ( Hyoung Jin Park,Yun Lyul Lee,Hyeok Yil Kwon,Yil Kim,Il Je Yu,Daniel r . Marshak ) 생화학분자생물학회 1992 BMB Reports Vol.25 No.3

The present study was performed to purify a BLI from the skin of frogs, B. orientalis inhabiting Kangwon-Do, Korea, and then determine its physiological activities and amino acid sequence. A substance that shows bombesin-like immunoreactivity (BLI) was partially purified from crude methanol extract of the frog skin by using a column of alkaline alumina and Sephadex G-10. BLI was further purified by using RP C18 preparative HPLC in which BLI was separated into 5 peaks. The major peak (BLI-K1) containing 65% of total BLI was subjected to purify as a single component by using sequential HPLC of SP-ion exchange and RP C18. Content of BLI in each fraction was monitored by RIA for which bombesin antiserum with a high titer and affinity to BBS was raised in a guinea pig. Eventually, 890 ㎍ of BLI-K1 was homogeneously purified from 420g of the skin of B. orientalis and it was not differentiated from synthetic BBS in RP C18, gel permeation and SP-ion exchange HPLC. In the physiological activities, BLI-K1 was identical to synthetic BBS in stimulation of gastrin release and exocrine pancreatic secretion including volume, protein, bicarbonate, amylase and chymotrypsin output in anesthetized rats. Furthermore, molecular weight and partial amino acid sequence of BLI-K1 was revealed to be identical to synthetic BBS. Therefore, it is concluded from the above results that the skin of B. orientalis contains the same BBS that has been isolated from the skin of European Bombina.

강원도 지역에 서식하는 무당개구리에서 생물학적 활성을 지닌 Bombesin 유사 Peptide에 관한 연구

박형진,이윤렬,권혁일,김일,유일재,Park, Hyoung-Jin,Lee, Yun-Lyul,Kwon, Hyeok-Yil,Kim, Yil,Yu, Il-Je 생화학분자생물학회 1992 한국생화학회지 Vol.25 No.3

본 실험에서는 강원도 지역에 집단으로 서식하고 있는 한국산 무당개구리(Bombina orientalis) 피부에서 bombesin 유사 peptide를 순수정제하여 생리활성과 amino acid 서열을 측정하고자 하였다. 무당개구리의 피부를 methanol에 담가 bombesin 유사반응물질(BLI)을 추출한 다음 alkaline alumina에 이은 Sephadex G-10 겔 크로마토그래피와 RP C18 preparative HPLC로 부분정제하였다. 부분정제시 여러 종류의 BLI가 출현하므로 본 연구에서는 전체 BLI의 65%를 점유하는 peak(BLI-K1)를 RP C18 및 SP-이온교환 HPLC를 이용하여 순수정제하였다. 피부조직 420 g에서 $890\;{\mu}g$의 BLI-K1를 순수정제하였으며, 이것은 RP C18, 겔 투과 그리고 SP-이온교환 HPLC 모두에서 합성 bombesin(BBS)과 동일한 정체시간을 나타내었다. 생리활성에서도 BLI-K1은 마취한 흰쥐에서 혈장 gastrin 농도와 혜장 단백질, 중탄산이온, amylase 및 chymotrypsin 분비량을 모두 유의하게 증가시켜 합성 BBS와 동일한 활성을 나타내었다. 또한 BLI-K1의 분자량 및 C-terminal의 11개 amino acid 서열이 합성 BBS과 동일하였기 때문에 한국산 무당개구리의 피부에도 유럽산 무당개구리의 피부에 존재하는 것과 동일한 bombesin이 존재하는 것으로 생각된다. The present study was performed to purify a BLI from the skin of frogs, B. orientalis inhabiting Kangwon-Do, Korea, and then determine its physiological activities and amino acid sequence. A substance that shows bombesin-like immunoreactivity (BLI) was partially purified from crude methanol extract of the frog skin by using a column of alkaline alumina and Sephadex G-10. BLI was further purified by using RP C18 preparative HPLC in which BLI was separated into 5 peaks. The major peak (BLI-K1) containing 65% of total BLI was subjected to purify as a single component by using sequential HPLC of SP-ion exchange and RP C18. Content of BLI in each fraction was monitored by RIA for which bombesin antiserum with a high titer and affinity to BBS was raised in a guinea pig. Eventually, $890\;{\mu}g$ of BLI-K1 was homogeneously purified from 420g of the skin of B. orientalis and it was not differentiated from synthetic BBS in RP C18, gel permeation and SP-ion exchange HPLC. In the physiological activities, BLI-K1 was identical to synthetic BBS in stimulation of gastrin release and exocrine pancreatic secretion including volume, protein, bicarbonate, amylase and chymotrypsin output in anesthetized rats. Furthermore, molecular weight and partial amino acid sequence of BLI-K1 was revealed to be identical to synthetic BBS. Therefore, it is concluded from the above results that the skin of B. orientalis contains the same BBS that has been isolated from the skin of European Bombina.

적출한 고양이 위(胃) 평활근 절편의 전기적 및 기계적 활동에 미치는 Bombesin의 영향과 그 작용기전

박형진(Park, Hyoung-Jin),권혁일(Kwon, Hyeok-Yil),서상원(Suh, Sang-Won),김정미(Kim, Jeong-Mi),이태형(Lee, Tae-Hyung) 대한생리학회 1990 대한생리학회지 Vol.24 No.1

bombesin의 생물학적 활성중 하나는 위장관의 평활근을 수축시키는 작용이다. 그러므로, 본 실험에서는 bombesin이 위장관의 운동성과 관계가 깊은 평활근의 전기적 활동에 미치는 영향과 신경기전을 밝히고자 하였다. 고양이 60마리로부터 urethane마취하에 위를 적출한 다음 대만 쪽에서 체부와 유문부가 포함된 평활근 절편을 얻었으며 또한 체부에서 윤상근 절편을 얻었다. 평활근 절편을 Krebs-Ringer 용액으로 채워진 기록용기에 넣고 Ag-AgCl전극을 사용하여 체부와 유문부에서 서파를 기록하는 한편 윤상근 절편의 자발적 수축을 기록하였다. 기록용기 속의 용액에는 5% ψCo₂ψ를 내포한 ψO₂ψ를 계속 공급하였으며, 용액의 온도는 ψ36℃ψ가 유지되도록 하였다. 기록용기 속에서 1시간 동안 안정시킨 다음 서파빈도와 수축빈도가 일정하여지면 bombesin과 그 유도체, substance P와 그 유도체 그리고 몇가지 종류의 신경차단제를 각각 투여하여 다음과 같은 결과를 얻었다. 1) bombesin은 ψ10^-9 Mψ에서부터 ψ3 X 10^-8 Mψ 사이의 농도에서 서파빈도와 수축빈도를 농도-의존적으로 증가시켰다. 2) bombesin 유도체인 ψD-leu¹³-ψ (CH₂NH)-D-leu¹⁴-bombesinψ은 서파빈도를 증가시키는 bombesin의 작용을 억제하였다. 3) 서파빈도를 증가시키는 bombesin의 작용에 대하여 tetrodotoxin과 hexamethonium은 억제적으로 작용하였으나 atropine, phentolamine 그리고 propranolol은 이렇다할 영향을 비치지 않았다. 4) 서파빈도를 증가시키는 bombesin의 작용에 대하여 substance P 유도체인 ψD-pro²-D-trp^7,9-substance Pψ는 억제적으로 작용하였다. 5) sunstance P 자체는 서파빈도에는 영향을 미치지 않았다. 이상의 결과로 보아 (1) bombesin은 적출한 고양이 위 평활근의 서파빈도와 체부 윤상근의 수축빈도를 증가시키며, (2) bombesin은 신경-근 연접에서 acetylcholine이나 noradrenalin을 신경전달물질로 사용하지 않는 내원성 신경을 거쳐 서파빈도를 증가시키는 것으로 생각된다. (3) 그러나, bombesin이 서파의 발생빈도를 증가시키는 과정에 substance P를 신경전달물질로 사용하는 신경이 개재하는 것 같지는 않았다. It has been reported that bombesin induces contraction of the smooth muscle of the gastrointestinal tract. Thus, the present investigation was undertaken to see an influence of bombesin on electrical activity of the gastric smooth muscle, since electrical activity is associated with contractile activity in the smooth muscle of the stomach. Smooth muscle strips ψ(5 X 1.5 cm)ψ that included the corpus and antrum were prepared from the ventral and dorsal portion of the feline stomach along the greater curvature. Circular muscle strips ψ(1 X 0.3 cm)ψ of the corpus were also obtained. Electrical activity of the corpus and antrum of the muscle strip was monophasically recorded by using Ag-AgCl capillary electrodes placed on the circular muscle layer. Contractile activity of the circular muscle strip was also recorded. The recordings were performed in Krebs-Ringer solution that was continuously aerated with O₂ containing 5% Co₂, and kept at ψ36℃ψ. Dose-related responses of electrical activity and contractility to bombesin was studied after frequency of slow waves and contraction of each strip reached to a steady state. An action of D-leu¹³-ψ (CH₂NH)-D-leu¹⁴-bombesin, tetrodotoxin, hexamethonium, atropine, phentolamine or propranolol on the effect of bombesin was also observed. 1) Bombesin increased frequency of slow waves and contractions dose-dependently at concentrations from ψ10^-9 M to 3 X 10^-8 Mψ. 2) The bombesin analogue at a concentration of ψ3 X 10^-7 Mψ antagonized the effect of bombesin on frequency of slow waves. 3) The effect of bombesin on frequency of slow waves was inhibited by tetrodotoxin ψ(10^-6 M)ψ and hexamethonium ψ(10^-3 M)ψ but unaffected by atropine ψ(10^-6 M)ψ, phentolamine ψ(10^-5 M)ψ and propranolol ψ(10^-5 M)ψ. 4) The effect of bombesin on frequency of slow waves was blocked by the substance P analogue at a concentration of ψ10^-5 Mψ. 5) Substance P at a concentration of ψ10^-5 Mψ failed to change frequency of slow waves. It is concluded from the above results that bombesin increases the frequency of slow waves as well as contractions of the smooth muscle strip from the feline stomach, and the effect of bombesin might be mediated by non-cholinergic or non-adrenergic mechanism at neuromuscular junction. However, enteric nerves that have substance P as a neurotransmitter do not appear to participate in the action of bombesin on frequency of slow waves.

E. coli DNA 절단과 mutagenicity에 대한 동충하초의 영향

이완희(Wanhee Lee),권혁일(Hyeok Yil Kwon),박진서(Jinseu Park),최수영(Soo Young Choi),이길수(Kil Soo Lee) 한국독성학회 1999 Toxicological Research Vol.15 No.3

Cordyceps militaris is one of the parasitic fungi Cordyceps sp. and used for Chinese traditional herbal medicine. Some components of Cordyceps sinensis extract such as cordycepin, certain polysaccharides and even it's crude extract are significantly effective on the immune system, enzyme inhibition, reveal anticancer and antifungal activity in animal experimental system. Protecting activity of Cordyceps militaris extract (CME) against DNA damage and antimutagenic activity of CME were investigated in microbial test system and in DNA fragmentation experiment. CME inhibited not only chromosomal DNA damage in E. coli, but also daunorubicin-induced plasmid DNA damage. It was observed that DNA damage inhibition in vitro by CME resulted from the inactivation of daunorubicin by CME, but not from cellular DNA protection by CME. In vivo mutagenicity test system in E. coli, CME did not repair DNA damage induced by 4-nitroquinoline-n-oxide (4NQO), but it caused the 4NQO inactivation which leads to inhibit 4NQO-induced β-galactosidase synthesis in SOS-chromotest. From the correlation between the inhibition of in vitro DNA fragmentation with the inhibition of cellular DNA damage in vivo, it is suggested that CME has an inhibitory effect on the DNA damaging action of daunorubicin and on the mutagenicity of 4NQO in E. coli test system.

Chemical Modification of Tryptophan Residue in Bovine Brain succinic Semlaldehyde Reductase

홍정우,전성규,반재훈,박진수,권혁일,조성우,최수영,Hong, Joung-Woo,Jeon, Seong-Gyu,Bahn, Jae-Hoon,Park, Jin-Seu,Kwon, Hyeok-Yil,Cho, Sung-Woo,Choi, Soo-Young The Korean Society for Integrative Biology 1997 Korean journal of biological sciences Vol.1 No.4

Incubation of an NADPH-dependent succinic semialdehyde reductase from bovine brain with N-bromosuccinimide (NBS) resulted in a time-dependent loss of enzyme activity. The inactivation followed pseudo-first-order kinetics with the second-order rate constant of $6.8\times{10}^3$ $M^-1$ $min^{-1}$. The inactivation was prevented by preincubation of the enzyme with substrate succinic semialdehyde, but not with coenzyme NADPH. There was a linear relation-ship between oxindole formation and the loss of enzyme activity. Spectro-photometric studies indicated that about one oxindole group per molecule of the enzyme was formed following complete loss of enzymatic activity. It is suggested that the catalytic function of succinic semialdehyde reductase is modulated by binding of NBS to a specific tryptophan residue at or near the substrate binding site of the enzyme.

갑상선기능항진증환자에서 소장운동성의 동태 변화

김연근(Yeon Keun Kim),서정은(Jung Eun Suh),임규성(Kyu Sung Rim),유재영(Jae Young Yoo),이영천(Young Cheon Lee),김교명(Kyo Myeong Kim),권혁일(Hyeok Yil Kwon),박형진(Hyoung Jin Park) 대한내과학회 1990 대한내과학회지 Vol.38 No.2

It is well-known that hyperthyroidism is associated with gastrointestinal (GI) motility disorders, such as frequent defecations and diarrhea. However, few studies have done a manometric analysis of GI motility, particularly the migrating motor comples (MMC