| Summary: | <span style="font-variant: small-caps;">d</span>-serine has been observed in submandibular gland tissue in rats, but its functions remain to be clarified. Oral administration of <span style="font-variant: small-caps;">d</span>-serine, but not <span style="font-variant: small-caps;">l-</span>serine, increased its concentrations in the submandibular gland and pilocarpine-induced salivary secretion. In vivo microdialysis was used to collect the <span style="font-variant: small-caps;">d</span>- and <span style="font-variant: small-caps;">l-</span>enantiomers of amino acids from local interstitial fluid in the rat submandibular gland. The proportion of the <span style="font-variant: small-caps;">d</span>-form of serine in interstitial fluid was higher than that in plasma or saliva. Perfusion of the rat submandibular gland with <span style="font-variant: small-caps;">d-</span>serine and <span style="font-variant: small-caps;">l-</span>glutamic acid via the submandibular gland artery resulted in a significant increase in salivary secretion after stimulation of muscarinic receptors with carbachol. In vivo microdialysis applied to the submandibular glands of rats showed that infusion of <span style="font-variant: small-caps;">d-</span>serine along with <span style="font-variant: small-caps;">l-</span>glutamate through the microdialysis probe significantly elevated acetylcholine levels in local interstitial fluids in the submandibular glands of anesthetized rats as compared to that with <span style="font-variant: small-caps;">l-</span>glutamate alone in an <i>N</i>-methyl-<span style="font-variant: small-caps;">d-</span>aspartate receptor glycine site antagonist-sensitive manner. These results indicate that <span style="font-variant: small-caps;">d-</span>serine augments salivary secretion by increasing acetylcholine release in the salivary glands.
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