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Exp Physiol ; 90(2): 189-93, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15572461

ABSTRACT

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.


Subject(s)
Cystic Fibrosis/diagnosis , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Saliva/metabolism , Salivary Gland Diseases/diagnosis , Salivary Glands/metabolism , Acetylcholine/administration & dosage , Animals , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Isoproterenol/administration & dosage , Mice , Mice, Inbred CFTR , Mice, Knockout , Salivary Gland Diseases/drug therapy , Salivary Gland Diseases/etiology , Salivary Glands/drug effects , Salivation/drug effects , Treatment Outcome
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