Phosphorylation-independent internalisation and desensitisation of the human sphingosine-1-phosphate receptor S1P3.

Here we demonstrate that phosphorylation of the sphingosine-1-phosphate (S1P) receptor S1P(3) is increased specifically in response to S1P. Truncation of the receptor's carboxyl-terminal domain revealed that the presence of a serine-rich stretch of residues between Leu332 and Val352 was essential to observe this effect. Although agonist-occupied wild-type (WT) S1P(3) could be phosphorylated in vitro by G-protein-coupled receptor kinase 2 (GRK2), a role of S1P(3) phosphorylation in controlling S1P(3)-G(q/11) coupling was excluded since A) a phosphorylation-resistant S1P(3) mutant desensitised in a manner indistinguishable from the WT receptor and was phosphorylated to a greater extent than the WT receptor by GRK2 in vitro, and B) co-expression with GRK2 or GRK3 failed to potentiate S1P(3) phosphorylation. S1P(3) phosphorylation was also not required for receptor sequestration away from the cell surface. Together, these data suggest that S1P(3) function is not subject to conventional regulation by GRK phosphorylation and that novel aspects of S1P(3) function distinct from classical G-protein coupling and receptor internalisation may be controlled its carboxyl-terminal domain.

In-office vital tooth bleaching--what do lights add?

Aqueous hydrogen peroxide (H2O2) has been used clinically at 30% to 35% levels to lighten teeth for many years, but the process has required multiple visits. Heat and light have been used empirically in attempts to catalyze H2O2 decomposition and speed tooth lightening. The contribution of bleaching lights (LumaArch, Optilux 500, and Zoom!) to act as catalysts for lightening teeth was studied in 83 pairs of contralateral anterior maxillary and mandibular teeth on 15 human subjects. Split-arch design using centrals, laterals, and canines on one side treated with bleach plus light, were compared with contralateral teeth using bleach alone. Three researchers trained in the use of the Vitapan 3D-Master Shade Guide took shades with independently agreement within 0.5 value-chroma sum 89% of the time throughout the study Laboratory tests determined bleach gel chemistry, bleach light output, and effects on the bleaches of light alone and heat alone. Results showed that the three test lights did not lighten teeth more than their bleach gels alone. All teeth lightened to nearly the same degree (1.7 color increments), but LumaArch required 60% less time and Zoom! used 1/3 lower H2O2 concentration. Laboratory tests indicated that the proprietary chemicals mixed into each bleach gel just before use acted as catalysts and were probably responsible for more rapid lightening produced by LumaArch gel, and need for less H2O2 in Zoom! gel. Neither the heat produced by the accessory lights, nor the light output itself were responsible for catalytic activity with any of the three systems tested. Collectively, the data demonstrate positive effects from chemical catalysts added to bleaching gels. No output from any of the lights resulted in heat or light that catalyzed the gels.