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3. Inner and outer portions of colonic circular muscle: ultrastructural and immunohistochemical changes in rat chronically treated with otilonium bromide.

Author

Chiara Traini, Maria Simonetta Faussone-Pellegrini, Stefano Evangelista, Katia Mazzaferro, Gianluca Cipriani, Paolo Santicioli, and Maria Giuliana Vannucchi

Subjects
Medicine, Science
Abstract

Rat colonic circular muscle, main target of otilonium bromide (OB) spasmolytic activity, is subdivided in an inner and outer portion. Since the inner one is particularly rich in organelles involved in calcium availability (caveolae, smooth endoplasmic reticulum, mitochondria), the expression of specific markers (Caveolin-1, eNOS, calreticulin, calsequestrin) in comparison with the outer portion was investigated. The possible changes of these organelles and related markers, and of muscarinic receptors (Mr2) were then studied after OB chronic exposition. Rats were treated with 2-20 mg/kg/OB for 10 or 30 days. Proximal colon was processed by electron microscopy, immunohistochemistry, and western blot. In colon strips the stimulated contractility response to muscarinic agonist was investigated. The inner portion showed a higher expression of Caveolin-1 and Mr2, but not of eNOS, calreticulin and calsequestrin, compared to the outer portion. Chronic OB treatment caused similar ultrastructural and immunohistochemical changes in both portions. Organelles and some related markers were increased at 10 days; Mr2 expression and muscle contractility induced by methacholine was increased at 30 days. The present findings: 1) provide new information on the immunohistochemical properties of the inner portion of the circular layer that are in favour of a role it might play in colonic motility distinct from that of the outer portion; 2) demonstrate that chronically administered OB interferes with cell structures and molecules responsible for calcium handling and storage, and modifies cholinergic transmission. In conclusion, chronic OB administration in the colonic circular muscle layer directly interacts with the organelles and molecules calcium-related and with the Mr2.

Published
2014
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22. NMR structure of Urotensin Peptide Asp-c[Cys-Phe-(N-Me)Trp-Lys-Tyr-Cys]-Val in SDS solution

Author

Brancaccio, D., primary, Carotenuto, A., additional, Merlino, F., additional, Billard, E., additional, Yousif, A.M., additional, Di Maro, S., additional, Abate, L., additional, Bellavita, R., additional, D'Emmanuele di Villa Bianca, R., additional, Santicioli, P., additional, Marinelli, L., additional, Novellino, E., additional, Hebert, T.E., additional, Lubell, W.D., additional, Chatenet, D., additional, and Grieco, P., additional

Published
2019
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23. NMR structure of Urotensin Peptide Asp-c[Cys-Phe-Trp-(N-Me)Lys-Tyr-Cys]-Val in SDS solution

Author

Brancaccio, D., primary, Carotenuto, A., additional, Merlino, F., additional, Billard, E., additional, Yousif, A.M., additional, Di Maro, S., additional, Abate, L., additional, Bellavita, R., additional, D'Emmanuele di Villa Bianca, R., additional, Santicioli, P., additional, Marinelli, L., additional, Novellino, E., additional, Hebert, T.E., additional, Lubell, W.D., additional, Chatenet, D., additional, and Grieco, P., additional

Published
2019
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24. Tachykinin receptors and intestinal motility

Author

Catalioto, R M, Criscuoli, M, Cucchi, P, Lippi, A, Meini, S, Patacchini, R, Renzetti, A R, Santicioli, P, Zagorodnyuk, V, Giachetti, A, Lecci, A, Tramontana, M, Giuliani, S, and Maggi, C A

Published
1997

27. Gender-related differential effect of tachykinin NK2 receptor-mediated visceral hyperalgesia in guinea pig colon

Author

Bellucci, F., Bueno, Lionel, Bugianesi, R., Crea, A., D'Aranno, V., Meini, Stephania, Santicioli, P., Tramontana, M., Maggi, C. A., Pharmacology Department, University, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Menarini Ricerche S.p.A, Partenaires INRAE, and Menarini Richerche S.p.A

Subjects
Male, Colon, brain, [SDV]Life Sciences [q-bio], Guinea Pigs, Thiophenes, localization, substance-p, sex, Animals, Sex Characteristics, binding-sites, Dipeptides, Receptors, Neurokinin-2, Visceral Pain, Colitis, Research Papers, irritable-bowel-syndrome, Disease Models, Animal, publication, Trinitrobenzenesulfonic Acid, Hyperalgesia, 5-ht3 antagonist, Female, neurokinin, pharmacology
Abstract

International audience; Background and PurposeThe tachykinin NK2 receptor antagonist ibodutant is under Phase III clinical investigation to treat female patients with irritable bowel syndrome. The aim of this study was to investigate the NK2 receptor-related gender specificity in a model of colitis. Experimental ApproachColitis was induced by rectal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS, 0.5mL, 30mgmL(-1) in 30% ethanol) in female and male guinea pigs. Electromyographic recording of the responses to colorectal distension (CRD) was made 3days later. Ibodutant (0.33 , 0.65, 1.9 and 6.5mgkg(-1)) was given s.c., 30min before CRD. Release of neurokinin A and substance P from isolated mucosal and smooth muscle tissues following treatment with KCl (80mM) or capsaicin (10M) was measured by EIA. Plasma pharmacokinetics of ibodutant following a single s.c. administration (0.73 or 2.1mgkg(-1)) were measured over 24h. Key ResultsIbodutant did not affect abdominal contractions in control animals. After TNBS-induced colitis, ibodutant prevented the increased visceral hypersensitivity to CRD in females, at lower doses than in males. Ibodutant pharmacokinetics did not differ between females and males. Tachykinins release was greater in smooth muscle than in mucosal samples. Capsaicin-stimulated release of tachykinins from inflamed mucosal samples from females was significantly lower than in males. Conclusions and ImplicationsIbodutant prevented abdominal nociception in a model of visceral hypersensitivity in guinea pigs with a greater efficacy in females than in males. Our results highlight a gender-related difference in colonic visceral hypersensitivity and mucosal nerve activation.

Published
2015
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29. DESIGN AND SYNTHESIS OF N-METHYL DERIVATIVES OF UROTENSIN-II

Author

MERLINO, FRANCESCO, DI MARO, SALVATORE, YOUSIF, ALI MUNAIM, Campiglia P., Meini S., Santicioli P., Maggi C. A., NOVELLINO, ETTORE, GRIECO, PAOLO, Kokotos G., Cordopatis P., Merlino, Francesco, DI MARO, Salvatore, Yousif, ALI MUNAIM, Campiglia, P., Meini, S., Santicioli, P., Maggi, C. A., Novellino, Ettore, and Grieco, Paolo

Subjects
Urotensin II, METHYLATION, Peptide Synthesi
Abstract

Human Urotensin-II is an undecapeptide (hUT-II, H-Glu-Thr-Pro-Asp-[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) which was identified as a potent vasoconstrictor that binds with high affinity to UT receptor. The cysteine-linked cyclic region, hUT-II(4-11), is responsible for the biological activity and has been widely used to elucidate the Structure-Activity Relationship of hUT-II. With the aim to investigate the role of hydrogen bond and the effects of a peptide backbone constraint on binding affinity and biological activity, we have designed and synthesized new analogues by multiple N-Methylation of hUT-II(4-11) backbone amide bonds. All the peptides were performed by a novel synthetic approach, in which the introduction of N-methyl groups occur during regular solid-phase peptide synthesis. On these new ligands we evaluated the binding affinity and biological activity at the UT receptor and performed preliminary NMR conformational studies.

Published
2012

31. P5U and urantide modifi ed at position 7 with TPI

Author

Auriemma L., Campiglia P., Monterrey Gomez I., Santicioli P., Maggi C. A., Sala M., Rovero P., d'Emmanuele diVilla Bianca R., CAROTENUTO, ALFONSO, NOVELLINO, ETTORE, SORRENTINO, RAFFAELLA, GRIECO, PAOLO, Auriemma, L., Campiglia, P., Monterrey Gomez, I., Santicioli, P., Maggi, C. A., Sala, M., Rovero, P., Carotenuto, Alfonso, Novellino, Ettore, d'Emmanuele diVilla Bianca, R., Sorrentino, Raffaella, and Grieco, Paolo

Published
2008

47. Sensory denervation with capsaicin reduces the liver collagen deposition induced by common bile duct obstruction in rats

Author

Casini, A., Lippe, I. T., Stefano Evangelista, Geppetti, P., Santicioli, P., Urso, C., Maggi, C. A., and Surrenti, C.

Subjects
Cholestasis, Common Bile Duct Diseases, Body Weight, Urinary Bladder, Proteins, Rats, Inbred Strains, Substance P, Rats, Eating, Hydroxyproline, Liver, Animals, Collagen, Neurons, Afferent, Capsaicin, Biliary Tract, Serum Albumin
Published
1991

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