Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Tachykinins: Role in Human Gastrointestinal Tract Physiology and Pathology

Author(s): Giovanna Improta and Maria Broccardo

Affiliation: Dipartimento di Fisiologia Umana e Farmacologia"V. Erspamer", Universita di Roma "La Sapienza", P.le A. Moro, 5 - 00185 Roma, Italia.

Abstract:

Tachykinins (TKs) and their receptors (NK1, NK2 and NK3), which are diffusely expressed in the human gastrointestinal tract, represent an endogenous modulator system regulating enteric secretomotor functions, inflammatory and immune responses, and visceral hypersensitivity, mainly during pathological gut diseases. Pathophysiological implications of TKs in the digestive tract include changes in TK innervation, in the expression of TKs and TK receptors, which result in inflammation- and immune-induced disturbances of gut functions, such as dysmotility (diarrhoea/constipation), secretory diarrhoea and visceral hyperalgesia. Increasing evidence correlates all these TKergic system abnormalities with gastrointestinal diseases of different etiology (i.e. inflammatory bowel diseases, irritable bowel syndrome). Accordingly, TK receptors have been identified as novel targets for the development of new therapeutic agents for clinical use. Available preclinical findings have shown that TK antagonists could counteract the most significant symptoms characterizing these gut diseases.

Keywords: neurokinin A, peristalsis, immunoreactivity, idiopathic chronic constipation, pyloric sphincter, Irritable bowel syndrome

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Article Details

VOLUME: 7
ISSUE: 8
Page: [1021 - 1029]
Pages: 9
DOI: 10.2174/138945006778019354
Price: $58