Colonic glycoprotein secretion and calmodulin-acceptor proteins in the reserpine-treated rat.
The rate of radioactive precursor-labeled colonic glycoprotein secretion in chronically reserpine-treated versus saline-injected control rats was examined. Everted colonic sacs prepared from reserpine-treated rats were found to be hypersecretory, exhibiting a basal rate of glycoprotein secretion that was threefold higher than control everted sacs. Furthermore, glycoprotein secretion in control tissue was stimulated by the secretagogue carbachol, and this stimulation was precluded by 10 microM trifluoperazine, the calmodulin antagonist. Reserpine-treated tissue, in contrast, was refractory to treatment with carbachol as well as trifluoperazine. While reserpine-treated and control colonic mucosae were demonstrated to contain equivalent levels of calmodulin via radioimmunoassay, reserpine-treated tissue was determined to lack two calmodulin-acceptor proteins with molecular weights of 29 and 47 kilodaltons. The data suggest that the mechanism by which reserpine elicits this cystic fibrosislike, hypersecretory state of glycoprotein secretion within the colonic mucosa entails the loss of calmodulin function in the regulation of this secretory process. We speculate that the biochemical defect present in cystic fibrosis could also entail such a loss of calmodulin function in the regulation of glycoprotein secretion.
Brady
R C
RC
Karnaky
K J
KJ
Dedman
J R
JR
D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology*
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D006023:Glycoproteins; D012110:Reserpine; D010749:Phosphoprotein Phosphatases