Diphenylhydantoin: An Alternative Ligand of a Glucocorticoid Receptor Affecting Prostaglandin Generation in A/J Mice

Abstract

Evidence for the binding of 5,5-diphenylhydantoin and glucocorticoids to a common receptor is presented for pulmonary and hepatic cytosols and thymocytes of A/J female mice. The 5,5-diphenylhydantoin-protein complex is absorbed by DNA cellulose, and is incorporated into nuclei, 5,5-Diphenylhydantoin, like glucocorticoids, inhibits the production of prostaglandins in thymocytes. Thus a common receptor is probably responsible for the inhibitory and teratogenic effects of these drugs.

Phenytoin in Wound Healing

“…Phenytoin may also interfere with the cortisol stimulation of collagenase synthesis centrally via the pituitary adrenal axis 54 or by competitive antagonism of the glucocorticoid receptor. 64 A number of the clinical studies indicate that phenytoin decreases the bacterial load of wounds. 5 ,6,19,24.26 Topical phenytoin was reported to eliminate S. aureus, Escherichia coli, Klebsiella spp., and Pseudomonas spp.…”

Inhibition of Programmed Cell Death in Mouse Embryonic Palate in Vitro by Cortisol and Phenytoin: Receptor Involvement and Requirement of Protein Synthesis

“…In our first study of the association between DPH teratogenicity and the glucocorticoid receptor, we demonstrated the blocking of [ 3H]dexamethasone incorporation into human embryonic palatal cells by 0.5 pM DPH (25). Recently, we have lNHIBITION OF CELL DEATH BY CORTISOL AND PHENYTOIN presented evidence that DPH and glucocorticoids bind to a common receptor which is responsible for the inhibition of prostaglandin generation and the teratogenic effects of these drugs ( 19). In view of these findings, we demonstrate in this report that DPH, like cortisol, inhibits the programmed cell death in the palatal medial edge epithelium in vitro and that this inhibition is also reversed by cortexolone and cycloheximide.…”

Phenytoin can accelerate the healing process after experimental myocardial infarction?

“…This phenomenon coincided with our discoveries in rat heart tissue. Katsumata et al [35] had reported that phenytoin can function as an alternative ligand of glucocorticoid receptor, inhibiting the generation of prostaglandin, which may exert a complex influence on inflammatory responses. Experimental inhibition of some components of matrix metalloproteinases (MMPs) seems to be beneficial to early post-infarction remodeling process [36,37].…”