Interactions of intestinal mediators in the mode of action of cholera toxin.
Cholera toxin (CT) and prostaglandin E2 (PGE2) increased the synthesis of 3',5'-cyclic adenosine monophosphate (cAMP) in rabbit intestinal mucosa, which appeared to be responsible for inducing the release of 5-hydroxytryptamine (5-HT) from enterochromaffin cells into the intestinal lumen. With isolated intestinal cells, CT induced the synthesis of PGE2 more efficiently from epithelial cells than from lamina propria cells; however, the basal amount of this eicosanoid produced by lamina propria cells was approximately six-fold more than that formed by the epithelial cells. The CT-induced stimulation of arachidonate metabolism appeared to be generalised in nature, as PGF2 alpha and leukotrienes were synthesised in addition to PGE2. Injection of dibutyryl cAMP into the intestinal lumen in vivo markedly reduced both basal levels of PGE2, as well as CT-induced levels of PGE2, released into the luminal fluid. Similarly, when biopsy samples of tissue from rabbit intestinal loops, challenged in vivo with dibutyryl cAMP, were washed and incubated in vitro, the amount of PGE2 synthesis remained below basal levels. In contrast, when biopsy samples of normal small intestinal tissue were exposed in vitro to dibutyryl cAMP, PGE2 synthesis increased. Thus, cAMP appeared to down-regulate the levels of intestinal eicosanoids in vivo, despite its innate capacity to evoke PGE2 synthesis from mucosal tissue in vitro. Thus, the data indicate that CT-induced mediators exhibit interactive effects that alter their cellular concentrations, that in turn could affect the biological responses.
Peterson
J W
JW
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555-1019.
Lu
Y
Y
Duncan
S
S
Cantu
J
J
Chopra
A K
AK
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012701:Serotonin / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms
D012701:Serotonin; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D015232:Dinoprostone