The difference in saliva/plasma concentration ratio(S/P ratio)of urea between mandibular and parotid glands in dogs was investigated in detail by a technique of retrograde ductal injection of HgC12.In every dog,four kinds of saliva[untreated(control)mandibular and parotid saliva,HgC12-treated mandibular and parotid saliva]were collected under pilocarpine stimulation of salivation. The following results were obtained.(1)It was verified in this study that S/P ratios of urea and Na+ were significantly increased in HgC12-treated mandibular saliva.(2)S/P ratios of urea and Na+in HgC12-treated parotid saliva were also significantly higher than those in untreated saliva.These results suggested that parotid salivary urea is also reabsorbed in the striated duct of dogs. (3)In untreated glands,the mean Cpr/CM ratio of urea(the ratio of urea concentration in parotid saliva to that in mandibular saliva)was about 1.65.This ratio tended to decrease toward unity in the HgC12-treated gland.Therefore,it was suggested that the striated duct might play an important role in the gland-specific difference of S/P ratios of urea between the salivary glands of dog. Keywords鈥endogenous urea;salivary excretion mechanism;mandibular gland;parotid gland;striated duct;gland-specific difference;HgCl2 retrograde injection;dog Saliva levels of drugs or chemicals have been used for pharmacokinetic studies and therapeutic drug monitoring.3-6)Regarding the salivary excretion mechanism of drugs chemicals,it has been considered that most of them are excreted into saliva by a passi transport process obeying pH-partition theory(Matin's equation).7'8)In this laboratory, has been reported that the observed values of saliva/plasma concentration ratios(S/P ratic for indomethacin,9'phenobarbita1,10)5-fluorouracill 11)and urea12)do not always agree wi the estimated values according to Matin's equation,that a gland-specific difference in the S ratios is observed between parotid and mandibular-sublingual salivas of dogs,and th this difference can not be explained quantitatively by Matin's equation.Therefore,it w considered to be important to investigate the salivary excretion mechanism in detail to pern a rational assessment of the role of saliva in relation to pharmacokinetic studies al therapeutic drug monitoring.With respect to salivary excretion of endogenous or exogenous urea,other investigators have studied only parotid saliva of man,dog and rat,and reported that the mean S/P ratio was about 0.7 but varied with the salivary flow rate.13-15)In our previous studies,salivary excretion of urea as a model compound has been studied using parotid,12)mandibularsublingual,12)mandibular16.17)and sublingual16)saliva of dog.It was shown that:1)S/P ratios of urea in parotid,mandibular-sublingual,mandibular and sublingual salivas were about 0.7,0.45,0.3 and 1.25,respectively,suggesting the existence of a gland-specific difference,12'16) 2)these results on S/P ratios of urea could not be explained by Matin's equation,12)3)S/P ratios of urea in mandibular saliva are no...