The mammalian nervous system constantly evaluates internal and environmental temperatures to maintain homeostasis and to avoid thermal extremes. Several members of the transient receptor potential (TRP) family of ion channels have been implicated as transducers of thermal stimuli, including TRPV1 and TRPV2, which are activated by heat, and TRPM8, which is activated by cold. Here we demonstrate that another member of the TRP family, TRPV4, previously described as a hypo-osmolarity-activated ion channel, also can be activated by heat. In response to warm temperatures, TRPV4 mediates large inward currents in Xenopus oocytes and both inward currents and calcium influx into human embryonic kidney 293 cells. In both cases these responses are observed at temperatures lower than those required to activate TRPV1 and can be inhibited reversibly by ruthenium red. Heat-evoked TRPV4-mediated responses are greater in hypo-osmotic solutions and reduced in hyperosmotic solutions. Consistent with these functional properties, we observed TRPV4 immunoreactivity in anterior hypothalamic structures involved in temperature sensation and the integration of thermal and osmotic information. Together, these data implicate TRPV4 as a possible transducer of warm stimuli within the hypothalamus.

Allylation of /3-keto esters or malonates was carried out in good yields under neutral conditions by using allylic carbonates in the presence of palladium-phosphine catalyst. Although simple ketones, esters, nitriles, and sulfones hardly react with allylic carbonates, -alkenyl or -aryl ketones, esters, nitriles, and sulfones were also allylated by using palladium-bis(diphenylphosphino)ethane catalyst under neutral conditions.We have reported the reaction of (v-allyljpalladium chloride (1) with carbonucleophiles such as malonates, acetoacetates, and enamines as a new method for carbon-carbon bond formation1 (Scheme I, eq 1). Later, in situ formation of (T-allyl)palladium complexes 2 as in-

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