Extracellular Ca2+ regulates dentin formation, but little information is available on this regulatory mechanism. We have previously reported that sensory denervation reduces dentin formation, suggesting a role for sensory nerves in tooth mineralization. The G protein-coupled Ca2+-sensing receptor (CaR) is expressed in dorsal root ganglia and perivascular sensory nerves in mesenteric arterioles, and activation of these receptors by Ca2+ has been shown to induce vascular relaxation. The present study determined CaR expression in tooth dental pulp (DP), sensory axons, and trigeminal ganglion (TG) as well as the effect of increased [Ca2+]e or a calcimimetic on tooth blood flow. The distribution of CaR, studied by immunochemistry, RT-PCR, and Western blot, indicates abundant expression of CaR in sensory axons in the jaws, TG, and DP. Restriction analysis of PCR products with specific endonucleases showed the presence of CaR message in TG and DP, and Western blotting indicates the expression of mature and immature forms of the receptor in these tissues. Pulpal blood flow, measured by laser-Doppler flowmetry, increased by 67% +/- 6% (n = 12) following receptor stimulation with 5 mM Ca2+, which was completely inhibited by 5 microM IBTx, a high-conductance KCa channel blocker indicating a mechanism involving hyperpolarization. NPS R-467 (10 microM) increased blood flow by 85% +/- 18% (n = 6), suggesting regulation through the CaR. Our results suggest that the CaR is present in sensory nerves, DP, and TG and that an increase in Ca2+ in the DP causes vasodilatation, which may contribute to accumulation of Ca2+ during dentin mineralization.