The distribution of gamma-aminobutyric acid (GABA) receptor subunits such as GABA_AR-gamma1 and GABA_AR-gamma2, and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type receptor subunits such as GluR-1, GluR-2/3 and GluR-4, and N-methyl-D-aspartic acid (NMDA) type subunits such as NR1 were investigated by immunocytochemistry. Furthermore, the roles of these amino acids, GABA and glutamate, on salivation were analyzed in the rat submandibular and sublingual glands. Some similarities were observed in the distribution patterns of GABA_A type receptors and AMPA-receptors. In the submandibular ganglion cells, collecting ducts and striated ducts, these subunits were expressed strongly ; however, there were some differences in their expression patterns between the submandibular and sublingual gland acinor cells. Since these receptor subunits were expressed in the acinor cell bodies of the submandibular gland, they were not expressed in the acinor cells but were expressed in the my
oepithelial cells in the sublingual gland.
On the other hand, no NR1 expression was observed. To examine the roles of GABA and glutamate in salivation, the submandibular and sublingual gland were perfused partially with Ringer Is solution via a facial artery to avoid systemic influence, and substrates were infused into the perfusion solution. No salivary secretion was evoked by GABA or glutamate infusion in the absence of electrical stimulation (2-3 V,5 msec, 20 Hz). Salivary flow evoked by electrical stimulation of the chorda-lingual nerve caused significant inhibition by GABA (10^<-6>,10^<-5>,10^<-4> and 10^<-3>M) and the GABAAR agonist muscimol (10^<-3> and 10^<-6>M) (n : 6, P<0.05).
Such GABA-induced inhibition was antagonized by the GABA_AR antagonists bicuculline (BCC ; 10^6 and 10^<-3> M) and picrotoxin (PTX ; 10^<-6> and 10^<-3> M). On the other hand, salivary flow evoked by electrical stimulation (8-10 V,5 msec, 20 Hz) of the superior cervical ganglion. (SCG) was not affected by GABA.While high doses of glutamate (10-1 M) and NMDA (10^<-1>M) showed no effects on salivary flow despite application of electrical stimulation, AMPA at a high concentration (10^<-1>M) significantly inhibited salivary secretion (n : 6, P<0.05). These studies revealed that inhibitory and excitatory amino acid receptors such as GABA^A and AMPA type receptors are coexpressed in the rat salivary glands, and that GABA inhibits salivary secretion via GABA^A receptors which may act with acetylcholine. However, the role of glutamate in salivation remains unclear despite the presence of AMPA type receptors. The present findings suggest that glutamate does not act alone but with other substances such as peptides and/or other amino acids.