Interstitial cells of Cajal in the subserosa (ICC-SS) of the guinea-pig proximal colon were studied by immunohistochemistry for c-Kit receptors and by transmission electron microscopy. These cells were distributed within a thin layer of connective tissue space immediately beneath the mesothelium and were multipolar with about five primary cytoplasmic processes that divided further into secondary and tertiary processes to form a two-dimensional network. Ultrastructural observations revealed that ICC-SS were connected to each other via gap junctions. They also formed close contacts and peg-and-socket junctions with smooth muscle cells. Three-dimensional analysis of confocal micrographs revealed that the cytoplasmic processes of ICC-SS had contacts with interstitial cells in the longitudinal muscle layer. Taking account of the location and peculiar arrangement of the ICC-SS and the main functions of the proximal colon, i.e. the absorption and transport of fluids, we suggest that the superficial network of ICC-SS acts as a stretch receptor to detect circumferential expansion and swelling of the colon wall and triggers the contraction of the longitudinal muscle to accelerate the drainage of fluids from the colon.

Interstitial cells of Cajal (ICC) form specialized networks in the gastrointestinal tract that coordinate cellular communications between nerves and smooth muscle cells. However, little is known about ICC in the gut mucosa or submucosa. Here, we report for the first time that Kit-immunoreactive ICC are associated with the submucosal (Meissner's) plexus of the Guinea-pig stomach. In longitudinal sections along the greater curvature of the gastric corpus, short spindle-shaped ICC of the submucosal plexus (ICC-SP) were located around the PGP9.5-immunoreactive nerve elements in the submucosa. Observations of whole-mount preparations clearly demonstrated Kit-immunoreactive bipolar or multipolar cells with long cytoplasmic processes about 100 mu m in length. Such cells had typical characteristics of ICC, confirming that they were not mast cells, which are also Kit-immunoreactive residents of the submucosal connective tissue space. Although some ICC-SP surrounded parts of the submucosal plexus, they did not appear to form wide extensions of the cellular network, suggesting that they acted locally. The demonstration of ICC-SP in the submucosal connective tissue space suggests that they may contribute to the regulation of secretion, absorption and transportation of fluids in the mucosa. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Interstitial cells of Cajal (ICC) form specialized networks in the gastrointestinal tract that coordinate cellular communications between nerves and smooth muscle cells. However, little is known about ICC in the gut mucosa or submucosa. Here, we report for the first time that Kit-immunoreactive ICC are associated with the submucosal (Meissner's) plexus of the Guinea-pig stomach. In longitudinal sections along the greater curvature of the gastric corpus, short spindle-shaped ICC of the submucosal plexus (ICC-SP) were located around the PGP9.5-immunoreactive nerve elements in the submucosa. Observations of whole-mount preparations clearly demonstrated Kit-immunoreactive bipolar or multipolar cells with long cytoplasmic processes about 100 mu m in length. Such cells had typical characteristics of ICC, confirming that they were not mast cells, which are also Kit-immunoreactive residents of the submucosal connective tissue space. Although some ICC-SP surrounded parts of the submucosal plexus, they did not appear to form wide extensions of the cellular network, suggesting that they acted locally. The demonstration of ICC-SP in the submucosal connective tissue space suggests that they may contribute to the regulation of secretion, absorption and transportation of fluids in the mucosa. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

The distribution and ultrastructure of the interstitial cells of Cajal (ICC) has been examined in the small intestine of the frog Xenopus laevis, as the physiological significance of these cells remains obscure in amphibians and other lower vertebrates. The present study has revealed the existence of a special type of interstitial cell in the tunica muscularis of the small intestine of Xenopus; this cell is characterized by the presence of numerous caveolae, many small mitochondria, and the formation of intercellular connections with the same type of cell. Since these ultrastructural features are shared with mammalian ICC, the cells in the small intestine of Xenopus probably correspond to ICC. These cells also form close contacts with neighboring smooth muscle cells and with nerve varicosities containing accumulations of synaptic vesicles. These cellular networks are likely to be involved in the transmission of nerve impulses to muscle cells, as has been suggested for mammalian tissues. However, true gap junctions have not been detected; they occur neither between the same type of cells nor between the putative ICC and smooth muscle cells. The widespread distribution of ICC or equivalent cells in different groups of vertebrates, together with the conservation of their ultrastructural features, suggests that they differentiated early in vertebrate evolution to play key regulatory roles in gastrointestinal movement.

The distribution and ultrastructure of the interstitial cells of Cajal (ICC) has been examined in the small intestine of the frog Xenopus laevis, as the physiological significance of these cells remains obscure in amphibians and other lower vertebrates. The present study has revealed the existence of a special type of interstitial cell in the tunica muscularis of the small intestine of Xenopus; this cell is characterized by the presence of numerous caveolae, many small mitochondria, and the formation of intercellular connections with the same type of cell. Since these ultrastructural features are shared with mammalian ICC, the cells in the small intestine of Xenopus probably correspond to ICC. These cells also form close contacts with neighboring smooth muscle cells and with nerve varicosities containing accumulations of synaptic vesicles. These cellular networks are likely to be involved in the transmission of nerve impulses to muscle cells, as has been suggested for mammalian tissues. However, true gap junctions have not been detected; they occur neither between the same type of cells nor between the putative ICC and smooth muscle cells. The widespread distribution of ICC or equivalent cells in different groups of vertebrates, together with the conservation of their ultrastructural features, suggests that they differentiated early in vertebrate evolution to play key regulatory roles in gastrointestinal movement.

The morphological features of interstitial cells of Cajal (ICC) in the gastrointestinal (GI) tract are described based on observations of laboratory animals including mice, rats and guinea-pigs, using immunohistochemical staining for Kit and electron microscopy. ICC show a specific distribution, arrangement and cell shape depending on their location within various regions and tissue layers of the GI tract. Hence they are classified into several subtypes. The stomach shows distinct regional variations in the distribution of subtypes of ICC from the cardia to pylorus, whereas the small intestine and colon both seem to retain nearly the same distribution pattern of subtypes of ICC throughout each organ. All subtypes of ICC share common ultrastructural features, such as the presence of numerous mitochondria, abundant intermediate filaments, and formation of gap junctions with the same type of cells and with smooth muscle cells. In addition, depending on their species and anatomical location, some subtypes of ICC show some features typical of smooth muscle cells including a basal lamina, caveolae, subsurface cisterns and dense bodies. ICC are somewhat heterogeneous morphologically. A question is raised on a special relationship between their ultrastructural features and dependency on Kit/stem cell factor system. As the neuromediator function of ICC, reciprocal distribution of ICC and gap junctions in the muscle coat is demonstrated by the comparison of Kit immunoreactive cells and gap junction protein connexin 43 in both small intestine and colon.

Using an embryoid body (EB) culture system, we have made a functional organlike cluster: the "gut" from embryonic stem (ES) cells (ES gut). There are many types of ES clusters, because ES cells have a pluripotent ability to develop into a wide range of cell types. Before inducing specific differentiation by exogenously added factors, we characterized comprehensive physiological and morphological properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and exhibits spontaneous contractions [mean frequency: 13.5 +/- 8.8 cycles per min (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth muscle cells were identified with electron microscopy. ICC frequently formed close contacts with the neighboring smooth muscle cells and occasionally formed gap junctions with other ICC. Widely propagating intracellular Ca2+ concentration oscillations were generated in the ES gut from the aggregates of c-Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in ICC, and electrical slow waves were recorded for the first time. These events were nifedipine insensitive, as in the mouse gut. Our present results indicate that the rhythmic pacemaker activity generated in ICC efficiently spreads to smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut. The present characterization of physiological and morphological properties of ES gut paves the way for making appropriate models to investigate the origin of rhythmicity in the gut.

Using an embryoid body (EB) culture system, we have made a functional organlike cluster: the "gut" from embryonic stem (ES) cells (ES gut). There are many types of ES clusters, because ES cells have a pluripotent ability to develop into a wide range of cell types. Before inducing specific differentiation by exogenously added factors, we characterized comprehensive physiological and morphological properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and exhibits spontaneous contractions [mean frequency: 13.5 +/- 8.8 cycles per min (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth muscle cells were identified with electron microscopy. ICC frequently formed close contacts with the neighboring smooth muscle cells and occasionally formed gap junctions with other ICC. Widely propagating intracellular Ca2+ concentration oscillations were generated in the ES gut from the aggregates of c-Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in ICC, and electrical slow waves were recorded for the first time. These events were nifedipine insensitive, as in the mouse gut. Our present results indicate that the rhythmic pacemaker activity generated in ICC efficiently spreads to smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut. The present characterization of physiological and morphological properties of ES gut paves the way for making appropriate models to investigate the origin of rhythmicity in the gut.

The distribution of different subtypes of interstitial cells of Cajal (ICC) in the tunica muscularis of the stomach of wild-type and W/W-v mice was studied by immunohistochemical staining for Kit. Special attention was also given to the distribution of the gap junction protein connexin 43 (Cx 43) immunoreactivity. Kit-immunoreactive cells of the circular and longitudinal muscle layers (ICC-CM and ICC-LM) were densely distributed throughout the cardia, fundus, the squamous epithelial portion of the corpus and the pylorus, but they were decreased in number within the glandular epithelial portion of the corpus. Kit-immunoreactive cells of the myenteric region (ICC-AP) emerged slightly proximal to the squamous-glandular epithelia] transition and increased in number towards the pylorus. Kit-positive cells were also observed at the submucosal border of the circular muscle layer (ICC-SM). ICC-CM and ICC-LM were not observed in the stomachs of W/W-v mice, but a few ICC-AP were observed in the pylorus. Cx 43 immunoreactive deposits were only sparsely distributed in the circular muscle layers of the cardia, fundus and the squamous epithelial portion of corpus. However, the Cx 43 immunoreactive deposits were densely distributed in the glandular epithelial portion of the corpus that contained fewer ICC-CM. Cx 43 immunoreactive deposits were rare in the circular muscle layer of the pylorus. No Cx 43 immunoreactivity was detected in the longitudinal muscle layer throughout the whole stomach. The distribution of Cx 43 immunoreactivity in the W/W-v mouse stomach was almost the same as in wild-type mice. The functional significance of each type of ICC at each region is discussed in reference to regional differences in the distribution of both ICC and Cx 43, and differences between wild-type and W/W-v mice.

The distribution of different subtypes of interstitial cells of Cajal (ICC) in the tunica muscularis of the stomach of wild-type and W/W-v mice was studied by immunohistochemical staining for Kit. Special attention was also given to the distribution of the gap junction protein connexin 43 (Cx 43) immunoreactivity. Kit-immunoreactive cells of the circular and longitudinal muscle layers (ICC-CM and ICC-LM) were densely distributed throughout the cardia, fundus, the squamous epithelial portion of the corpus and the pylorus, but they were decreased in number within the glandular epithelial portion of the corpus. Kit-immunoreactive cells of the myenteric region (ICC-AP) emerged slightly proximal to the squamous-glandular epithelia] transition and increased in number towards the pylorus. Kit-positive cells were also observed at the submucosal border of the circular muscle layer (ICC-SM). ICC-CM and ICC-LM were not observed in the stomachs of W/W-v mice, but a few ICC-AP were observed in the pylorus. Cx 43 immunoreactive deposits were only sparsely distributed in the circular muscle layers of the cardia, fundus and the squamous epithelial portion of corpus. However, the Cx 43 immunoreactive deposits were densely distributed in the glandular epithelial portion of the corpus that contained fewer ICC-CM. Cx 43 immunoreactive deposits were rare in the circular muscle layer of the pylorus. No Cx 43 immunoreactivity was detected in the longitudinal muscle layer throughout the whole stomach. The distribution of Cx 43 immunoreactivity in the W/W-v mouse stomach was almost the same as in wild-type mice. The functional significance of each type of ICC at each region is discussed in reference to regional differences in the distribution of both ICC and Cx 43, and differences between wild-type and W/W-v mice.

Interstitial cells of Cajal in the circular (ICCCM) and longitudinal (ICC-LM) muscle layer of the rat gastric antrum and their innervation were studied ultrastructurally. Both ICC-CM and ICC-LM are characterized by many mitochondria, rough and smooth endoplasmic reticulum, caveolae, and formation of gap junctions with each other and with muscle cells, though ICC-LM tend to show more variable cytoplasmic features depending on section profiles. Close contacts between nerve terminals and both ICC-CM and ICC-LM are observed. These possible synaptic structures are characterized by: (1) accumulation of synaptic vesicles in nerve varicosities, (2) a narrow gap (about 20 nm) between pre- and postjunctional membranes, (3) lack of a basal lamina between pre- and postjunctional membranes, and (4) the presence of an electron-dense lining on the inner aspect of prejunctional membranes. Almost the same characteristics are observed between the nerve terminals and the muscle cells of both circular and longitudinal muscle layers of the same specimens. Therefore, we conclude that the smooth muscle cells of both circular and longitudinal layers of the rat antrum are directly and indirectly innervated via ICC. Their functional significance is discussed.

The shape, distribution, and ultrastructural features of interstitial cells of Cajal (ICC) of different tissue layers and organs of the rat and guinea-pig digestive tract were described and compared with the corresponding cells in other species including mice, dogs, and humans, as reported in the literature. By light microscopy, the best marker for ICC appeared to be immunoreactivity for c-Kit. Ultrastructurally, ICC were characterized by the presence of many mitochondria, bundles of intermediate filaments, and gap junctions, which linked ICC with each other. However, ICC were morphologically heterogeneous and had particular features, depending on their tissue and organ location and species. ICC in the deep muscular plexus of the small intestine and in the submuscular plexus of the colon were the most like smooth muscle cells, and had a distinct basal lamina and numerous caveolae. In contrast, ICC of Auerbach's plexus at all levels of the gastrointestinal tract were the least like smooth muscle cells. They most closely resembled unremarkable fibroblasts. ICC within the circular muscle layer were intermediate in form. In addition to the tissue specificity, some organ and species specificity could be distinguished. The structural differences between ICC may be determined by their microenvironment, including the effects of mechanical force, type of nerve supply, and spacial relationship with smooth muscle cells.

　蠕動運動のペースメーカーや神経筋興奮伝達の介在機能をもつカハールの介在細胞（ICC）は、消化管の部位に固有な運動を制御していることが推定され、その解析は消化管平滑筋運動の理解の上での重要な課題である。本研究では、胃の各領域、組織層におけるICCの分布を明らかにすると共に、ICC各亜型の細胞学的特性を知るため、マウスおよびラットの胃を材料に用い、免疫組織化学的ならびに電子顕微鏡的に検索した。　正常マウス胃の噴門、胃底、胃体重層扁平上皮部の良く発達した輪走および縦走筋層には多くのc-KIT陽性反応、即ち、ICCが観察されたが、筋層間神経叢には認められなかった。筋層間神経叢のICCは胃体腺上皮部への移行部より出現し始め、幽門部には非常に密度高く観察された。一方、gap junction 蛋白Cx43は、噴門、胃底、胃体重層扁平上皮部、幽門部を通じて、輪層筋層に散在性に弱く観察されたが、胃体腺上皮部では、高い密度で観察された。　これらの観察より、マウス胃では、ペースメーカー機能をもつ筋層間神経叢のICCが出現する胃体腺上皮が自律的蠕動運動の起始部にあたると推定された。また、噴門、胃底、胃体重層扁平上皮部、幽門部の輪走筋層の細胞間の電気的結合度は弱く、豊富なICCが神経信号の伝達に介在するものと推定された。他方、c-kitに 突然変異のあるW／Wvマウスでは、胃の全領域を通じて筋層内のICCは欠損する傍ら、幽門部の筋層間神経叢のICCは少数観察され、ICCの亜型によってc-kit/SCF 系に対する依存性に相違のあることが明らかとなった。　ラット胃を材料とした幽門部筋層の検索では、これまでに報告の無い縦走筋層内のICC に焦点を当て検索した。縦走筋内のICCは豊富なミトコンドリア、中間径フィラメント、カヴェオラを含み、同種細胞間、平滑筋とgap junctions を形成する点で、これまで報告されてきた輪走筋内のICC と共通する特徴もつことが示され、シナップス小胞を多量に含む神経終末と密接して観察された。他方、神経終末は平滑筋とも直接密接する像が観察されたことより、ラット胃幽門部の縦走筋は、ICCを介する間接支配と神経による直接支配との平行支配を受けるものと推定された。

　本研究では、消化管筋層に存在するカハールの介在細胞（ＩＣＣ）の刺激伝達装置としての機能を解析すると共に、各器官組織層に分布するＩＣＣの細胞組織学的分類を行い総括した。＊ ラット小腸深部筋神経叢の免疫組織化学的検索では、豊富な神経支配を受けている深部筋神経層のＩＣＣ（ＩＣＣ-ＤＭＰ）はＣｘ43抗体に陽性なgap junctionによって平滑筋と結合しており、gap juncitonを介した細胞網を通じて、刺激伝達機能の役割を担っているものと推定した。＊ また、消化管のＮＡＮＣ抑制性神経として知られているＮＯニューロンのＩＣＣ支配についての検索では、ラット小腸深部筋神経叢に沿ってＮＡＤＰＨ-diaphorase組織化学に陽性の強い反応が観察された。同様に処理した標本の電子顕微鏡観察では、ＩＣＣに密接してシナップス小胞を含む反応陽性の終末が観察された。また凍結切片によるＶＩＰ免疫染色では、深部筋神経叢に一致して強い陽性反応が規則的に観察された。以上の観察から、ＩＣＣはＮＯニューロンの運動支配を受け、筋とのgap junctionを介して刺激を伝達するものと推定した。また同一ニューロンにおけるＮＯとＶＩＰの混在の可能性についても考察した。＊ 一方、消化管各部位、各組織層の違いによるＩＣＣの細胞学的特性を系統的に整理するため、従来の研究成果を補完する微細構造学的検索を行った。その結果、ラットおよびモルモットでは、胃、小腸、結腸を通して、筋層間神経叢部に線維芽細胞に類似したＩＣＣ－ＡＰが認められたが、小腸深部筋神経叢部のＩＣＣ－ＤＭＰと結腸筋層下神経叢部のＩＣＣ－ＳＭＰにはカヴェオラや明瞭な基底膜が観察され、平滑筋に似た特徴が見られた。また、胃および結腸輪走筋層内のＩＣＣ－ＣＭでは、連続した基底膜は欠くもののカヴェオラは観察されるなど、両者の中間的な特徴が見られた。ＩＣＣ－ＤＭＰ，ＩＣＣ－ＳＭＰは勿論、胃、結腸のＩＣＣ－ＣＭにおいても、平滑筋とgap junctionを形成し、神経終末と密接することから、神経信号のmediatorとして働くものと推定した。

　消化管に内在し、蠕動運動の調節を行う筋層間神経叢は食道横紋筋部にも存在するが、この部位では迷走神経の直接支配を受けることが定説となっており、内在性神経叢の構造と機能については不明な点を多く残してきた。本研究では、食道筋層のほぼ全長にわたって横紋筋線維をもつモルモット食道を材料に用い、食道横紋筋部筋層間神経叢の微細構造を明らかにすることを目的として、電子顕微鏡的に検索を行った。　その結果、モルモット食道筋層間神経節は神経筋細胞、神経膠細胞およびそれらの突起が複雑に絡み合った緻密な神経網を形成し、中枢神経系組織に類似した特徴をそなえている一方、細部については食道固有の構造を持つことが明らかとなった。神経節への知覚性および介在性ニューロン入力の少ないことを示す神経終末の数や種類に乏しいこと、神経要素の疎な神経節の形状を整え機械的衝撃を緩衝すると推測される神経膠細胞の特異な層板状構造、等が観察された。また、迷走神経起源と考えられる有髄線維が、ミトコンドリアを豊富に含む軸索膨大部との連続性を持って神経節内に観察されたことは、知覚終末を示唆する貴重な観察結果と言える。NADPH-d反応の微細構造レベルの観察においては、多数の神経節細胞に反応が認められる一方、外来性神経束では軸索総数の約３％に反応が見られるのみであることから、この観察所見は、横紋筋支配のNADPH-d反応陽性線維が内在性由来であることを、更に支持するものと推定した。

本研究では、ペースメーカーとの密接な関係が報告されているc-kit receptorに注目し、消化管運動ペースメーカーとして提唱されているカハールの介在細胞（Interstitial Cells of Cajal; ICC）の細胞学的解析を目的とした。材料としてはc-kit遺伝子に突然変異をもち、消化管運動に異常のあることが知られているWs/Wsラットおよび同腹の正常ラット＋/＋を用い、消化管各部位におけるc-kit発現細胞の電子顕微鏡的観察による比較、検討を行った。　その結果、（a）筋層間神経叢のＩＣＣは、消化管の部位（胃、小腸、大腸）に拘らず、共通の微細構造（豊富なミトコンドリア、大きなgap-junctionの形成など）によって特徴ずけられることを確認した。また、これらの細胞はWs/Wsラットでは観察されなかった。（b）一方、小腸の深部筋神経叢及び大腸の筋層下神経叢のＩＣＣでは、上記の特徴に加え、基底膜、caveolaeを示したが、この細胞はWs/Wsラットでも観察された。以上の観察結果から、ＩＣＣは細胞学的に不均一な細胞群からなり、c-kitに対する依存度についても異なる細胞型を含むものと推定した。また筋層間神経叢のＩＣＣはペースメーカーとして機能するものと考えられるが、その他の部位のＩＣＣについては、更に慎重な検索、考察が必要なものと結論した。研究成果の発表1998年Horiguchi K. and Komuro T.Ultrastructural characterization of interstitial cells of Cajal in the rat small intestine using control and Ws/Ws mutant rats. Cell Tissue Res. 293, 277-284.

　ヒトを含む動物の食道筋層には、胃、小腸とは異なり横紋筋線維が存在し、骨格筋と同様、神経筋結合部が観察される。従来の定説によれば、これらの横紋筋の神経支配は迷走神経運動核に直接由来するものと考えられてきたが、よく発達した内在性の筋層間神経叢ニューロンの存在理由については疑問のままのこされてきた。ところで、最近の研究によれば、その内在性ニューロンによる筋支配の可能性が示唆されているが、その候補としてNOニューロンが注目されている。NOについては、Non-adrenergic Non-chorinergic(NANC)抑制ニューロンの働きが下部消化管において推定されているが、食道においては、その存在様態についても十分に明らかにされていない。　本研究では、食道の全長にわたるNOニューロンの分布様式、細胞組織学特徴について明らかにする事を目的として、モルモット食道を用い、Nitric oxide synthaseの証明と等価値を持つNADPH(nicotinamide adenine dinucleotide phosphate)-diaphorase活性の検出をする組織化学染色をおこなった。また、上記試料を電子顕微鏡用標本として作製し、微細構造レベルでのNOニューロンについても観察した。　NADPH-d染色陽性細胞(NOニューロン)は、食道全長を通じて多数存在しており、食道上部から下部にわたって変化する筋層間神経叢の構築を反映して分布することが証明された。食道筋層間神経叢は全体として疎で不規則な網目構造を呈するが、上部では神経節策と結合策との境界が不分明なほどNOニューロンは散在するのに対し、下部では神経節策内に限局して密集する。又、運動性と推定されているDogiel1型の細胞も多数みとめられた。電子顕微鏡による観察では、NOニューロンは、細胞質内の粗面小胞体、核膜に NADPH-d陽性反応を示す細胞として観察され、反応陰性の幾つかのタイプの軸策終末のシナップスを受ける一方、神経節内ではシナップス前構造としての明瞭な像を示さない。また筋層内には、内在性と推定される反応陽性の無髄神経線維束が多数認められた。これらの観察をもとに、食道筋層間神経叢のNOニューロンの生理的意義について考察した。

○研究の背景および目的 固体の生命維持に重要な消化管運動は，自律神経系による調節に加えて，内在するペースメーカーに依って支配されている。従来より，ペースメーカーの存在は，生理学的に知られるところであったが，その細胞学的根拠については不明であった。本研究ではペースメーカーの細胞学的特性および神経，筋要素との組織学的関係を明らかにし，ペースメーカー機能発現の形態学的根拠について検索した。○材料および方法 実験動物としてはモルモットの大腸を用い，標的細胞の微細構造，細胞骨格蛋白の性質を明らかにするため，電子顕微鏡的ならびに免疫組織学的に検索した。また，古典的記載との対照をはかるためヨウカ亜鉛－オスミウム酸（ZIO）法も併用した。○結果および考察 ZIO法にて固定，染色後，大腸の筋層を剥離，伸展標本として観察すると，粘膜下結合組織と輪走筋層との境界部によく発達した神経繊維網が黒染して現われ，これに付随して星形の細胞が認められる。この細胞は，数本の長い突起によって相互に連結し，細胞性の網状構造を作るが，その形状，構成は，消化管運動ペースメーカーとして現在推定されているカハールの介在細胞（Thuneberg, 1982）と酷似する。 同一の標本を電子顕微鏡用試料として再包理し，超薄切片として観察すると，標的細胞はZIOの沈殿物を含む細胞として容易に識別される。この細胞は，よく発達したコルジ装置，小胞体，ミトコンドリアを含み，基底膜は無く微細構造的には繊維芽細胞の特徴を有する。また，間葉系細胞に豊富に存在するビメンチン，フィラメントの抗体で染色するとZIO法にて描出された星形の細胞と同形の細胞が観察される。以上の結果より，モルモット大腸に見られるペースメーカー細胞は，間葉系由来の繊維芽細胞様細胞と推定した。