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- Title
Acetylcholine induces cytosolic Ca<sup>2+</sup> mobilization in isolated distal colonic crypts from normal and cystic fibrosis mice.
- Authors
Klaren, P. H. M.; Hardcastle, J.; Evans, S.; Colledge, W. H.; Evans, M. J.; Taylor, C. J.; Hardcastle, P. T.; White, S. J.
- Abstract
In intestinal biopsies from cystic fibrosis (CF) patients acetylcholine fails to elicit a chloride secretion response, and this observation can be explained by a defect in the Ca2+ signalling pathway in CF secretory cells. We tested the hypothesis that in CF intestine, the generation of an intracellular Ca2+ signal upon cholinergic stimulation is absent. A transgenic CF mouse model was used. Electrical measurements on intact jejunum and unstripped colon were performed in Ussing chambers. Intact distal colonic crypts were isolated, and the intracellular Ca2+ concentration was monitored using the Ca2+-sensitive dye fura-2. Acetylcholine increased the short-circuit current generated by wild-type jejunum and colon, but failed to induce a response in CF tissues. Acetylcholine caused a transient elevation in the intracellular Ca2+ concentration in colonic crypts from both wild-type and CF mice; the amplitude and timing of the response in CF crypts was indistinguishable from that in wild-type crypts. The response to acetylcholine was also observed in the absence of extracellular calcium, indicating intracellular stores as the source from which the cytosolic Ca2+ concentration increased. We conclude that the absence of a cholinergically-induced secretory response in CF intestine is not due to a defect in the generation of a Ca2+ signal in intestinal cells upon cholinergic stimulation.
- Publication
Journal of Pharmacy & Pharmacology, 2001, Vol 53, Issue 3, p371
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1211/0022357011775424