Abstract

Adrenergic agonists, acting through a specific Alpha2-receptor, have been shown to affect ileal ion transport in vitro. However, little is known about the intracellular events mediating this process or its regulatory role in the intact animal. These questions are key to understanding and developing new therapeutic approaches to diseases in which watery diarrhea may be a consequence of altered noradrenergic innervation of the intestinal mucosa. The present study proposes to (1) investigate the intracellular events that mediate Alpha2-adrenergic response in ileal mucosa, specifically adenylate cyclase and intracellular free calcium. A technique, using a calcium-selective, pH insensitive, fluorescent probe has been proposed to study changes in intracellular free calcium concentrations in both the intact tissue and isolated enterocytes; (2) Evaluate in the intact animal the role of noradrenergic innervation of the epithelium in the homeostatic regulation of intestinal water and electrolyte transport. Methods for measuring the extent of functionally relevant innervation will be established; and (3) Study two clinical entities, diabetic diarrhea and opiate withdrawal diarrhea, where there is reason to believe that the impaired noradrenergic innervation of the epithelium results in a secretory (or anti-absorptive) diarrhes. The methods proposed in (2) will be used to study this hypothesis in established animal models.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Unknown (R23)
Project #
5R23AM035096-02
Application #
3446127
Study Section
(GCN)
Project Start
1984-07-01
Project End
1985-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027