American Journal of Physiology: Cell Physiology, 2001-04, Vol.280 (4), p.C852-C858
2001
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Details
- Autor(en) / Beteiligte
- Titel
- Potent NK1 antagonism by SR-140333 reduces rat colonic secretory response to immunocyte activation
- Ist Teil von
- American Journal of Physiology: Cell Physiology, 2001-04, Vol.280 (4), p.C852-C858
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2001
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 1 Department of Veterinary Physiology and Biochemistry and 3 Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland; and 2 Department of Internal Medicine, Sanofi-Synthélabo, 92504 Rueil-Malmaison, France The potent neurokinin receptor 1 (NK 1 ) antagonist SR-140333 has previously been shown to reduce castor oil-induced secretion in animal models. The importance of tachykinins in neuroimmune control of secretion and the effect of SR-140333 on key points in this pathway were elucidated in the present study to determine the type of intestinal dysfunction best targeted by this antagonist. Rat colonic secretion and substance P (SP) release were determined in vitro with the use of Ussing chamber and enzyme immunoassay techniques. NK 1 receptors played a secretory role as receptor agonists stimulated secretion and SR-140333 antagonized the response to SP response (pK b = 9.2). Sensory fiber stimulation released SP and evoked a large secretion that was reduced by 69% in the presence of SR-140333 (10 nM). Likewise, mastocytes also released SP. The subsequent secretory response was reduced by 43% in the presence of SR-140333 (50 nM). SP was also released from granulocytes; however, this did not cause secretion. Functional NK 3 receptors were present in the colon as senktide stimulated secretion, an effect that was increased during stress. We conclude that NK 3 receptors may play a role in stress-related disorders, whereas NK 1 receptors are more important in mast cell/afferent-mediated secretion. afferent; granulocyte; irritable bowel syndrome; inflammatory bowel disease; mast cell
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0363-6143eISSN: 1522-1563DOI: 10.1152/ajpcell.2001.280.4.c852Titel-ID: cdi_pubmed_primary_11245602
- Format
- –
- Schlagworte
- Animals, Benzamides - pharmacology, Capsaicin - pharmacology, Colon - cytology, Colon - immunology, Colon - secretion, Colonic Diseases, Functional - drug therapy, Colonic Diseases, Functional - immunology, Electric Stimulation, Male, Mast Cells - immunology, Neurokinin A - pharmacology, Neurokinin-1 Receptor Antagonists, Peptide Fragments - pharmacology, Piperidines - pharmacology, Quinuclidines - pharmacology, Rats, Rats, Inbred Strains, Receptors, Neurokinin-1 - metabolism, Receptors, Neurokinin-2 - antagonists & inhibitors, Receptors, Neurokinin-2 - metabolism, Receptors, Neurokinin-3 - metabolism, Stress, Physiological - immunology, Stress, Physiological - metabolism, Substance P - analogs & derivatives, Substance P - pharmacology