Salivary secretion assay for drug efficacy for cystic fibrosis in mice.
Computerized assays on cultured cells ex vivo have been used to screen thousands of compounds for their effectiveness in correcting the basic physiological defect in cystic fibrosis (CF). While a number of these compounds appear promising, their effectiveness will almost certainly need to be demonstrated in animals before therapeutic tests in humans will be possible. We show herein that the function of salivary secretion in the mouse model for CF could be used as a simple, easy and rapid in vivo assay for drug effects. We demonstrate that salivary secretory capacity stimulated with a beta-adrenergic agonist closely reflects the genotype of origin. Specifically, the mean maximal secretory rate of saliva in normal wild type (+/+) mice was about 1.5 times higher than that of the mean rate in heterozygote (+/-) mice and more than 50 times greater than in CF (-/-) mice. Total saliva secreted per stimulated period obeyed a similar phenotype-genotype segregation. The data indicate that salivary secretory rates in CF mice could be used to assay potential drugs for their effectiveness in correcting the secretory defect in cystic fibrosis.
Best
John Adam
JA
University of California, San Diego, Department of Pediatrics, 9500 Gilman Drive, La Jolla, CA 92093-0831, USA. pquinton@ucsd.edu
Quinton
P M
PM
D000109:Acetylcholine / Q000008:administration & dosage; D000818:Animals; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007545:Isoproterenol / Q000008:administration & dosage; D051379:Mice; D018181:Mice, Inbred CFTR; D018345:Mice, Knockout; D012463:Saliva / Q000378:metabolism*; D012466:Salivary Gland Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects; D016896:Treatment Outcome
D007545:Isoproterenol; D000109:Acetylcholine