Adenylate cyclase in intestinal crypt and villus cells: stimulation by cholera enterotoxin and prostaglandin E1.

The secretory responses to cholera enterotoxin and prostaglandin E1 (PGE1) are dependent upon elevation of the intracellular levels of cyclic AMP. Although several previous reports have suggested that intestinal secretion due to cholera enterotoxin and PGE1 may be confined to the crypt cells, this matter has been incompletely resolved. These studies were undertaken to define the activity of adenylate cyclase in villus and crypt cells from rabbit and rat intestine, and to determine the influence of enterotoxin and PGE1 on this activity, Mucosal fractions were prepared from rabbit ileum with a planing device, and from rat distal small intestine by a vibration technique. In both species base line adenylate cyclase activity was greater in crypt than in villus cells. After exposure to cholera enterotoxin in vivo, adenylate cyclase activity was enhanced in all fractions prepared from rabbit ileum, and the response was most marked in villus cells. Furthermore, adenylate cyclase in membranes prepared from both rat villus and crypt intestinal cells was responsive to the in vitro addition of PGE1. The results of these studies indicate that both villus and crypt cells contain one of the important components required for the cyclic AMP-mediated secretory response, namely, a cholera enterotoxin and PGE1-sensitive adenylate cyclase activity. Since an increased level of cyclic AMP alone may not be sufficient to evoke a secretory response, these studies do not clarify the extent to which each of these major cell types may participate in cyclic AMP-mediated secretion.