흰쥐 난포의 성장과 퇴화에 따른 bcl-2 단백질 발현에 관한 면역조직화학적 연구

고필옥,정성윤,조경제,최완성,곽수동,Koh, Phil-ok,Jeong, Sung-yoon,Cho, Gyeong-jae,Choi, Wan-sung,Kwak, Soo-dong 대한수의학회 1999 大韓獸醫學會誌 Vol.39 No.1

In the mammalian ovary, follicular development and atresia continuously occur during the reproductive cycles. Follicular atresia occurs through granulosa cell apoptosis. Apoptosis is known as the physiological cell death, which is regulated by bcl-2 gene family. In the bcl-2 gene family, bcl-2 and bcl-xLong are known as inhibitors of apoptosis, whereas bax and bcl-xShort are known as inducer of apoptosis. We thought that bcl-2 protein is associated with follicular development and atresia. But it is not known that the distribution of cells containing bcl-2 protein during follicular development and atresia. Therefore, to examine the distribution of cells with bcl-2 protein during ovarian follicular development and atresia, the immunohistochemistry was used in the rat ovary. Bcl-2 immunoreactivity was localized in the interstitial cells, theca externa cells and granulosa cells around of antrum. All positive signals were observed in the cytoplasm of these cells. Positive signals were strongly observed in the interstitial and theca externa cells of growing antral follicles. While, positive signals were weakly observed in these cells from atretic antral follicles. Positive signals were very weakly observed in the granulosa cells of growing and atretic antral follicles. According to these data, we suggested that bcl-2 proteins which were strongly expressed in the interstitial cells and theca externa cells of growing antral follicles inhibit follicular atresia. And we purposed that bcl-2 proteins regulated follicular development and atresia through the action of bcl-2 gene family.

사람 태반에서 GnRH와 GnRH-receptor mRNAs의 발현

김명옥(Myeong Ok Kim),고필옥(Phil Ok Koh),조경제(Gyeong Jae Cho),김해석(Hae Suk Kim),이종학(Jong Hak Lee),김종화(Jong Hwa Kim),백원영(Won Young Paik),최완성(Wan Sung Choi) 대한체질인류학회 1998 해부·생물인류학 (Anat Biol Anthropol) Vol.11 No.1

본 연구는 사람 태반에서 GnRH 와 CnRH -receptor mRNAs 가 어느 세포에서 양현되는지 조사하고, 발현세포의 분포가 임신시기에 따라 어떻게 변화하는지를 조사하기 위하여 수행되었다. 임신중의 각 시기별 태반조직을 대상으로 GnRH 와 CnRH -receptor cDNA 에 대한 cRNA probe 흘 이용하여 tn Stf hybndlzation 을 시행 한 결과에서 다음과 갇은 소견을 얻었다. GnRH mRNA 는 모든 임신시기의 태반 조직내의 cytotrophoblasts, syncytiotrophoblasts, villous stromal cells 에서 동정되었다. GnRH mRNA signals 은 맡기로 갈수록 villous stromas 에서 강한 양성 반응이 관찰되었다. GnRH- receptor mRN A signals는 9-10주의 cytotrophoblasts 와 syncyhotrophoblasts 에서 강한 발현을 나타내었고 말기로 갈수록 감소되었다. GnRH 도 사람의 태반내에서 trophoblasts 에서 극소적 으로 생성되고, CnRH -receptor 는 GnRH 와 유사하게 태반융모의 trophoblast 에서 발현 된다. 또한, CnRB -receptor 가 임신유지에 필요한 융모악 성샘자극호르몬의 분비양상과 유사하게 생성되는 것으로 보아 GnRH 가 융오악 성생자극호르몬의 망성 벚 분비에 있어 조정인자로 작용할 가능성이 있있며, 그 작용에 있어 paracnne 또는 autocnne 역할을 항 것으로 생각된다.

Expression of Bcl-2 and Bax mRNAs During Follicular Development and Atresia in the Rat Ovary

고필옥(Phil Ok Koh),강상수(Sang Soo Kang),최완성(Wan Sung Choi),곽수동(Soo Dong Kwak),조경제(Gyeong Jae Cho) 대한해부학회 1999 Anatomy & Cell Biology Vol.32 No.1

포유류의 난소는 생식주기에 따라 난포의 성장 (follicular development)과 퇴화(follicular atresia)가 주기적으로 일어나며 이중 난포의 퇴화는 programed cell death인 apoptosis에 의해 일어난다. Apoptosis는 bcl-2 gene family에 의해 조절되며 이들 유전자 중 bcl-2는 apoptosis를 억제하는 유전자로, bax는 apoptosis를 유도하는 유전자로 알려져 있다. 본 연구에서는 미성숙한 흰쥐에 PMSG를 투여하여 난포의 성장과 퇴화를 유도한 후 이들 난포에서 bcl-2와 bax mRNA의 발현을 in situ hybridization으로 조사하였다. PMSG를 투여한 후 1일과 2일군에서는 대부분의 난포가 난포강을 형성하였고 과립세포가 균일하게 난자를 둘러싸고 있 었으며 투여후 3일군에서는 성장하는 난포와 난포의 형태가 일그러지고 과립세포층이 얇아지는 퇴화하는 난포들이 관찰되었다. 4일, 5일군에서는 난포의 과립세포층이 얇아지고 응축된 핵이 나타난 퇴화하는 난포들이 관찰되었는데 이들 퇴화하는 난포는 in situ DNA end labeling에 양성반응세포을 보였다. Bcl-2 mRNA에 대한 in situ hybridization에서는 성장난포와 퇴화난포의 기질세포 (interstitial cell), 난포막세포 (theca cell)에서 양성반응이 나타났고 PMSG를 투여한 후 1일, 2일군의 성장난포의 기질세포, 난포막세포에서 강하게 발현되었다. Bax mRNA는 성장난포와 퇴화난포의 기질세포, 난포막세포, 과립막세포 (granulosa cell)에서 양성반응이 나타났고 PMSG를 투여한 후 4일, 5일군의 퇴화난포의 기질세포, 난포막세포와 과립막세포에서 발현되었으므로 bcl-2와 bax의 비율이 세포의 운명을 결정하는데 중요한 역할을 한다는 사실을 확인 할 수 있었다. Bcl-2는 난포의 성장과 퇴화시 기질세포, 난포막세포에서 발현되어 난포의 퇴화를 억제하는 역할을 하며 bax는 퇴화하는 난포의 기질세포, 난포막세포와 과립막세포에서 발현되어 난포의 퇴화를 유도한다고 생각되었다. 따라서, bcl-2와 bax는 기질세포와 난포막세포에서 주로 합성되어 난포의 성장과 퇴화를 조절한다고 할 수 있다. In the mammalian ovary, follicular atresia occurs through apoptosis. Apoptosis is known as the physiological cell death, which is regulated by bcl-2 gene family. In the bcl-2 gene family, bcl-2/bcl-xLong is known as an inhibitor of apoptosis, whereas bax/bcl-xShort is known as an inducer of apoptosis. We thought that these genes are associated with follicular development and atresia. Therefore, the present study used a in situ hybridization to examine the expression of bcl-2 and bax mRNAs during ovarian follicular development and atresia induced by PMSG(15 IU) treatment in the immature rat ovary. Morphological changes were occurred with the manner of five days periodicity after PMSG treatment. One or two days after PMSG treatment, ovaries had growing follicles with antrum and healthy granulosa cells. Three days after treatment, some degenerating follicles which had thinner granulosa cell layers than growing follicles were observed. At day four and five after treatment, degenerating follicles which have pyknotic nuclei and thin distorted granulosa cell layers appeared. These atretic follicles showed positive reaction with in situ DNA end labelling which indicates apoptotic changes. This study showed that bcl-2 mRNA was expressed in the theca and interstitial cells. Growing follicles of one or two days have showed stronger bcl-2 mRNA signals than atretic follicles of four or five days in these cells. Bax mRNA was expressed in the theca cells, interstitial cells, and granulosa cells. Atretic follicles of four or five days showed stronger bax mRNA signals than growing follicles of one or two days in these cells. Expression of bcl-2 mRNA was increased in growing follicles while decreased in atretic follicles. In contrast, expression of bax mRNA was increased in atretic follicles while decreased in growing follicles. Therefore, we confirmed that follicular development and atresia were affected by the change in the ratio of bcl-2 and bax mRNAs. According to these data, we proposed that these two genes are associated with follicular development and atresia.

의과대학 학생의 맨눈해부학 지식에 대한 임상교수의 인식도 조사

임선주(Sun-Ju Im),감비성(Bee-Sung Kam),이상엽(Sang-Yeoup Lee),우재석(Jae-Seok Woo),이종태(Jong-Tae Lee),이상화(Sang-Hwa Lee),임학(Hak Im),조경제(Gyeong-Je Cho),백선용(Sun-Yong Baek) 대한체질인류학회 2014 해부·생물인류학 (Anat Biol Anthropol) Vol.27 No.4

의과대학과 의학전문대학원에 통합교육과정이 도입되면서 임상실습 기간의 확대로 기초의학의 강의 시간이 줄어들었으며, 대학에 따라서 맨눈해부학 교육의 시간과 내용은 상당한 차이를 보이고 있다. 이에 따라 재학생과 졸업생의 해부학 지식의 저하에 대한 우려가 제기되고 있다. 해부학 교수와 학습의 방향 설정의 기초 자료로 활용하기 위하여 임상실습 과정 학생들의 맨눈해부학 지식과 교육과정 내에서 해부학 교수법의 현 상태에 대하여 임상실습을 지도하는 임상 교수의 인식도에 대한 조사가 필요하였다. 부산·경남지역의 5개 의과대학에 근무하는 임상교수를 대상으로 학생들의 맨눈해부학 지식에 대한 인식도를 설문 조사하여 통계분석을 하였다. 임상교수의 입장에서 졸업생의 임상해부학 지식 정도(2.4±0.6)와 고학년 학생의 전반적인 해부학 지식(2.6±0.7)의 저하를 우려하였으며, 선택 집중해부실습(3.8±0.9)과 해부학 교육 시기 확대(3.3±1.0)에 긍정적이었다. 학생들의 전반적 국소해부학 지식의 수준에 대해서는 외과계열과 영상의학, 외과계열과 기타계열 사이에 유의한 차이를 보였으며(p?0.05), 외과 계열이 해부학 지식수준의 저하를 가장 우려하였다. 해부학교육 시기의 확대에 대해서는 영상의학이 내과, 외과 및 기타 계열과 유의한 차이를 보여 가장 긍정적인 응답을 하였다(p?0.001). 학생들이 해부학 지식이 낮은 원인으로는 임상맥락이 적은 해부학교육이 가장 높았으며, 그 다음으로 통합교육과정에 따른 해부학의 정체성 감소였다. There is concerns about the perceived decline in the knowledge of gross anatomy of the medical students and postgraduate trainees. It is partly caused by the introduction of integrated medical curriculum and the shortage of basic medical science program and the extension of clinical clerkship consequently. There is widespread variability in the teaching style and anatomical curricular content at the medical school in Korea. Despite these changes in the anatomical education, there have been few attempts to assess the opinions of senior clinical teachers on the state of anatomical knowledge of students and the place of anatomy teaching within the curriculum. We sought the views of the clinical teachers on the adequacy of the anatomical knowledge of current students and recent graduates of 5 medical schools in Pusan and Gyeongsang-Nam do areas. Most of the clinical teachers were of the opinion that current medical students have an insufficient anatomical knowledge. They indicated the causes of decline were the clinical irrelevant anatomical teaching content and weakness of identity of anatomy by the introduction of the integrated medical education program. There was widespread support for both the concepts of spreading anatomy teaching throughout the medical course, and an optional, clinically related final year student project in the anatomy.

The Changes in the Expression of γ-Aminobutyric Acid Related Enzymes in the Mouse Hippocampus Following Ketogenic Diet

노해숙(Hae Sook Noh),권오영(Oh-Young Kwon),윤혜정(Hae Jeong Yun),강상수(Sang Soo Kang),조경제(Gyeong Jae Cho),최완성(Wan Sung Choi) 대한해부학회 2007 Anatomy & Cell Biology Vol.40 No.3

케톤생성 식이요법은 항경련 약물에 반응하지 않는 난치성 소아간질에 오래 전부터 사용되고 있는 효과적인 치료 방법 중에 하나이다. 그러나 항경련 기전에 관해서는 현재까지 거의 알려져 있지 않다. 본 연구에서는 케톤생성 식이요법이 억제성 신경전달 물질인 GABA의 발현에 미치는 영향을 면역 조직 화학법과 노던 블랏팅으로 관찰하였다. 그 결과, 케톤생성 식이요법이 해마 내 GABA의 발현을 증가시키고, GABA transporter1(GABA-Tp)과 GABA transaminase (GABA-T) mRNA의 레벨을 감소시키는 것을 관찰할 수 있었다. 이러한 결과들로부터, 케톤생성 식이요법은 GABA의 재흡수를 억제하거나, 분해를 억제하여 연접 공간에서 GABA 수준을 증가시킴으로써 항경련 효과를 유도해 냄을 유추할 수 있었다. The ketogenic diet (KD) has been used to treat intractable childhood epilepsy. However, its mechanism of action remains unknown. In the present study, we examined the effects of KD on the expression of multiple constituents of the GABAergic system in the hippocampus through immunohistochemistry and northern blot analysis. From the results, we have shown that KD increased expression of GABA and decreased GABA transporter1 (GABATp) and GABA transaminase (GABA-T) mRNA levels in the hippocampus. These results suggest that the neuroinhibitory effect of KD may be mediated, at least in part, by the increment of GABAergic activity in the hippocampus. KD may increase the GABA levels in the synaptic space by limiting GABA reuptake and in the presynaptic nerve terminal by inhibiting GABA degradation.

Involvement of VEGF in Both Cell Apoptosis and Survival in the Retina of Type 2 Diabetic OLETF Rats

김영희(Young Hee Kim),최미영(Mee Young Choi),김윤숙(Yoon Sook Kim),노구섭(Gu Seob Roh),김현준(Hyun Joon Kim),강상수(Sang Soo Kang),최완성(Wan Sung Choi),조경제(Gyeong Jae Cho) 대한해부학회 2007 Anatomy & Cell Biology Vol.40 No.4

Vascular endothelial growth factor (VEGF)는 망막혈관장애, pericyte 손실, 망막신경세포사와 세포증식등을 포함한 당뇨병의 초기망막병변에 많은 영향을 미친다. 본 연구에서는 제2형 당뇨병 쥐의 망막에서의 세포사와 세포생존에 VEGF가 연계되어 있는지를 조사하였다. 실험에는 자발적인 제2형 당뇨병 모델의 하나인 28주령의 Otsuka Long-Evans Tokushima Fatty (OLETF)쥐들과 대조군으로 Long-Evans Tokushima Otsuka (LETO)쥐들의 망막이 이용되었다. 대조군에 비해 OLETF 쥐의 망막에서는 pericyte 손실의 증거와 함께 세포증식, 세포사, endothelial nitric oxide synthase (eNOS)와 VEGF의 증가가 확인되었다. 또한, OLETF 쥐의 망막에서의 세포사멸신호는 VEGF에 특이적인 세포에서 일부 확인되었지만, VEGF-independent eNOS 특이 세포에서는 전혀 관찰되지 않았다. 이 결과들은 제2형 당뇨병 OLETF 쥐의 망막에서 VEGF는 세포사와 eNOS 의존적 세포생존에 모두 관계하고 있음을 시사한다. Vascular endothelial growth factor (VEGF) is closely involved in early retinal pathology of diabetes, including blood-retinal barrier breakdown, pericyte loss, neuro-retinal apoptosis, and cell proliferation. This study examines the involvement of VEGF in cell apoptosis and survival in the retina of animals with type 2 diabetes. We used retinas from 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous type 2 diabetes, and Long-Evans Tokushima Otsuka (LETO) rats as controls. In parallel with evidence for pericyte loss, we found cell proliferation, apoptosis, and endothelial nitric oxide synthase (eNOS) (an indicator of endothelial cell proliferation/survival) and VEGF overexpression in the OLETF-retina, compared to control LETO. Furthermore, apoptotic signals were partly co-localized to only VEGF-positive cells in the OLETF-retina, but no apoptotic signals were found in VEGF- and eNOS-double-positive cells. These results suggest that upregulated VEGF is involved in apoptosis and eNOS-dependent cell survival in the retinas of type 2 diabetic rats.

Differential Effects of Antipsychotic Drugs on Dopamine D1 and D2 Receptor mRNAs in the Rat Brain

김명옥(Myeong Ok Kim),김윤숙(Yoon Sook Kim),박창환(Chang Hwan Park),양영애(Young Ae Yang),강상수(Sang Soo Kang),조경제(Gyeong Jae Cho),노구섭(Gu Seob Roh),최완성(Wan Sung Choi) 대한해부학회 2005 Anatomy & Cell Biology Vol.38 No.4

본 연구는 흰쥐 뇌의 조가비핵 (CPu), 기댐핵 (NAc), 후각결절 (OTu) 부위에서 항정신병약물(antipsychotics)에 의한 도파민 D1, D2 수용체 mRNA 발현양상의 변화를 알아보고자 하였다. Sprague-Dawley계의 흰쥐를 대상으로 정상군은 물, 실험군은 물을 대신하여 haloperidol (1mg/mL), sulpiride (40 mg/mL), clozapine(20 mg/mL)을 4주 동안 지속적으로 공급하였다. 이러한 약물의 처리는 도파민 D1, D2 mRNA 유전자 발현에 있어서 다른 결과를 나타내었다. Haloperidol, sulpiride는 흰쥐 뇌의 CPu, NAc, OTu 부위에서 도파민 D1, D2 수용체 mRNA 발현 증가를 유발하였고, Haloperidol 처리군이 sulpiride 처리군 보다 도파민 D1, D2 수용체 mRNA 발현양상이 증가한 것으로 관찰되었다. 하지만, clozapin의 처리는 동일한 부위에서 도파민 수용체 mRNA 발현양상이 적었다. 항정신병약물의 처리는 흰쥐 뇌에서 도파민 D1, D2 수용체 mRNA 발현에 차이 있는 결과를 나타내었다. 이상의 결과로 항정신병약물 처리는 도파민 농도 변화에 부분적으로 관여하는 것으로 생각된다. The principal aim of this study was to determine the effects of antipsychotics (haloperidol, sulpiride, and clozapine) on regulating dopamine (DA) D1 and D2 receptor mRNA levels in the rat caudate putamen (CPu), nucleus accumbens (NAc), and olfactory tubercle (OTu). Twenty male Sprague-Dawley rats (250 g) were treated with haloperidol (1mg/mL), sulpiride (40 mg/mL), clozapine (20 mg/mL), and the control group received only water. Drugs were administered orally for 4 weeks. Antipsychotic drugs had differential effects on DA D1 and D2 receptor gene expression. Haloperidol and sulpiride induced an increase of DA D1 and D2 receptor mRNA levels in the rat CPu, OTu, and NAc; haloperidol caused a greater increase than sulpiride. However, clozapine treatment had less effect on DA receptor mRNAs levels in the same area. Antipsychotic drugs differentially upregulated the expression of DA D1 and D2 receptor mRNAs in the rat brain. These changes may be related, at least in part, to changes of DA concentration following antipsychotics treatment.

Alterations of Tyrosine Hydroxylase and Choline Acetyltransferase in the Retina of the Diabetic Rat

최미영(Mee-Young Choi),김영희(Young-Hee Kim),김윤숙(Yoon-Sook Kim),남희(Hee Nam),유지명(Ji-Myung Yoo),최완성(Wan-Sung Choi),조경제(Gyeong-Jae Cho) 대한해부학회 2006 Anatomy & Cell Biology Vol.39 No.6

To investigate the effect of hyperglycemia on the visual system, we investigated the retinal dopaminergic and cholinergic systems using tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) in the rat retinas of streptozotocin (STZ)-induced diabetes. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg) to Sprague-Dawley rats (250~300 g). We first analyzed morphologic thickness changes in the several retinal layers of 6-week-old control and STZ-diabetic rats after H & E staining. To confirm whether TH and ChAT protein expressions changed, we carried out immunohistochemistry analysis and Western blotting. After induction of diabetes, significant changes were not shown in the retinal thickness at 6 weeks. TH and ChAT immunoreactivities were clearly detected in amacrine cells and sublaminas in the inner retina of both control and diabetic rats, showing continuously reduced positive amacrine cells in the retinas during diabetes. In addition, the decline in TH and ChAT protein expression was already present to a significant extent in the retina at 6 weeks in early diabetes. Our present study demonstrates the possibility that the observed alterations in TH and ChAT in the diabetic retina may cause the visual system changes in the retinal pathophysiology associated with diabetes mellitus. 본 연구에서는 고혈당이 시각의 dopaminergic 및 cholinergic system에 미치는 영향을 알아보기 위하여 streptozotocin (STZ)으로 유도한 당뇨병 모델 흰쥐의 망막에서 tyrosine hydroxylase (TH)와 choline acetyltransferase (ChAT)의 변화를 알아보았다. 당뇨병은 250~300 g Sprague-Dawley (SD) 흰쥐에 50 mg/kg STZ을 복 막내 주사하여 유도하였고 6주 후에 희생시켰다. H & E 염색을 통하여 정상쥐와 당뇨쥐 망막의 형태학적인 변화를 관찰하였고, 면역조직화학법과 western blotting을 이용하여 TH와 ChAT 단백질의 발현과 변화를 분석하였다. 당뇨병 유발 6주 후 흰쥐의 망막에서 뚜렷한 형태학적인 변화는 나타나지 않았으나 TH와 ChAT의 단백질 발현과 면역반응성의 유의적인 감소가 확인되었다. 본 연구는 TH와 ChAT의 변화가 초기 당뇨 흰쥐 망막의 시각시스템변화와 연관되어 있음을 시사한다.

흰쥐 난포의 성장과 퇴화에 따른 CDK inhibitor(CDI) p57 및 bcl-2 mRNA 발현

조경제,고필옥,곽수동,김명옥,이봉희,최완성,백상호 대한해부학회 1998 Anatomy & Cell Biology Vol.31 No.3

면역조직화학법을 이용한 Wistar-Kyoto Rat(WKY)와 Spontaneously Hypertensive Rat(SHR) 신장의 도파민 D₁와 D₂수용체의 분포

이종덕,고필옥,최완성,정순일,장세호,조경제 대한신장학회 1998 Kidney Research and Clinical Practice Vol.17 No.6

The kidney and balances of fluid and volume are the basic components of bloocl pressure control, and the kidney is the primary site that initiates the hypertensive process and is affected by hypertensive vascular disease. In the kidney, the dopamine is a potent natriuretic and vasodilating agent, participat- ing in renal sodium excretion and maintenance of cardiovascular homeostasis. And the dopamine receptors in central nervous system and peripheral organs were identified by physiological, biochernical and radioligand binding techniques. Rut previous morphological and biochemical studies have been unable to characterize or determine the tissue distri- bution of the dopamine receptor subtypes because no selective ligands are available yet. Furthermore, the cellular distribution of the dopamine receptor subtypes in the rat kidney is not demonstrated well. In the SHR, the ability of exogenous and endogenous renal dopamine to engender a natriuresis is impaired. Since renal dopamine levels in genetic models of hypertension are not lower than their normotensive controls, the impaired intrarenal paracrine effect of dopamine in these animal models of hypertension appears to be receptor or postreceptor mediated. And renal dopamine derives mainly from renal tubular dopamine production and to a lesser extent from dopaminergic nerves. The present study utilizes imrnunohistochemistry with specific antibodies to characterize the renal distribution of dopamine receptor subtypes and recognize the role of dopamine receptor defect in the pathogenesis of hypertension in 14-week-old WKY (mean HP 108+-5mmHg) and SHR(mean RP 174+-7 mmHg) kidneys. Also it utilizes antibody of tyrosine hyclroxylase(TH) to recognize the site of the dopamine production mediated by TH using light microscopic immunohistochemistry. In the immunohistochemistry of the WKY kidney, dopamine D1 receptor protein is localized to glomerulus, proximal tubule, distal tubule, renal vessels, cortical and medullary collecting duct. And in the SHR kidney, dopamine D1 receptor protein is localized to glomerulus, distal tubule, renal vessels, cortical and medullary collecting duct, and juxtaglomerular apparatus(JGA). But there is no demonstrable positive reaction in the proximal tubule and weakly positive reactions in the renal arterioles of SHR compared with WKY kidney. In the immunohisto-chemistry of the WKY kidney, dopamine D1 receptor protein is localized to glomerulus, proxirnal tubule, distal tubule, renal vessels, cortical and rnedullary collecting duct. And in the SHR kidney, dopamine D2 receptor protein is localized to glomerulus, distal tubule, renal vessels, cortical and medullary collecting duct, and JGA. So, there is no demonstrable positive reaction in the proximal tubule of SHR compared with WKY. In the glomerulus of the WKY and SHR kidneys, both dopamine D1 and D2 receptors are localized. In the in situ hybridization of the WKY and SHR kidneys, dopamine D and D receptors are only demonstrated at the renal vessels. The positive reaction to TH immunohistochemistry of the WKY and SHR kidneys is only observed in the renal medulla compared with negative reaction on the renal cortex. Considering the excretion of sodium up to 65-70% with volume expansion may be mediated by dopamine D1-like receptors in the proximal tubule, our immunohistochemistry findings for the dopamine receptors may support the failure of natriuretic response in the SHR due to an abnormal dopamine receptor. Also our results rnay mean that the glornerular filtration rate is mediated by both dopamine D1 and Dz receptors comparing with the previous studies that the glomerular filtration rate was mediated by dopamine D2 receptor. I'here are some differences in the receptors expressing sites on the previous radioligand binding and pharmacologic studies, but our results suggest that at least some of the renal dopamine DA and DAz receptors correspond structurally to the central dopamine D1 and D2 receptors. Finally the result of TH immunohisto-chemistry suggests that the production of dopamine in the proximal tubule is not mediated by TH.