title: NK receptors, Substance P, Ano1 expression and ultrastructural features of the muscle coat in Cav-1(-/-)  mouse ileum.
abstract: Caveolin (Cav)-1 is an integral membrane protein of caveolae playing a crucial role in various signal transduction pathways. Caveolae represent the sites for calcium entry and storage especially in smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Cav-1(-/-)  mice lack caveolae and show abnormalities in pacing and contractile activity of the small intestine. Presently, we investigated, by transmission electron microscopy (TEM) and immunohistochemistry, whether the absence of Cav-1 in Cav-1(-/-)  mouse small intestine affects ICC, SMC and neuronal morphology, the expression of NK1 and NK2 receptors, and of Ano1 (also called Dog1 or TMEM16A), an essential molecule for slow wave activity in gastrointestinal muscles. ICC were also labelled with c-Kit and tachykinergic neurons with Substance P (SP). In Cav-1(-/-)  mice: (i) ICC were Ano1-negative but maintained c-Kit expression, (ii) NK1 and NK2 receptor immunoreactivity was more intense and, in the SMC, mainly intracytoplasmatic, (iii) SP-immunoreactivity was significantly reduced. Under TEM: (i) ICC, SMC and telocytes lacked typical caveolae but had few and large flask-shaped vesicles we called large-sized caveolae; (ii) SMC and ICC contained an extraordinary high number of mitochondria, (iii) neurons were unchanged. To maintain intestinal motility, loss of caveolae and reduced calcium availability in Cav-1-knockout mice seem to be balanced by a highly increased number of mitochondria in ICC and SMC. Loss of Ano-1 expression, decrease of SP content and consequently overexpression of NK receptors suggest that all these molecules are Cav-1-associated proteins.
authors.affiliation: Department of Anatomy, Histology and Forensic Medicine, Section of Histology, University of Florence, Florence, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cipriani
authors.forename: Crenguta S
authors.initials: CS
authors.lastname: Serboiu
authors.forename: Mihaela
authors.initials: M
authors.lastname: Gherghiceanu
authors.forename: Maria Simonetta
authors.initials: MS
authors.lastname: Faussone-Pellegrini
authors.forename: Maria Giuliana
authors.initials: MG
authors.lastname: Vannucchi
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D021941:Caveolae / Q000378:metabolism / Q000648:ultrastructure; D051242:Caveolin 1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D005769:Gastrointestinal Motility; D007082:Ileum / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure*; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008931:Mitochondria, Muscle / Q000648:ultrastructure; D009119:Muscle Contraction; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000648:ultrastructure*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis* / Q000276:immunology; D018041:Receptors, Neurokinin-2 / Q000096:biosynthesis* / Q000276:immunology; D015398:Signal Transduction; D013373:Substance P / Q000276:immunology / Q000378:metabolism*
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D018118:Chloride Channels; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D013373:Substance P; D019009:Proto-Oncogene Proteins c-kit