Juan Pablo Huidobro-Toro

Investigation

Our laboratory is devoted to study the role of nucleotides including purines and pyrimidines such as ATP, ADP, UTP, UDP and adenosine, as novel extracellular autocrine/paracrine signals. ATP in particular is stored in synaptic vesicles of sympathetic nerve endings where it operates as a sympathetic co-transmitter acting together with noradrenaline. However, nucleotides are also released to the extracellular media, from almost all cells, by a variety of stimuli such as: hypoxia, ischemia, swelling, or mechanical stress; their mechanism of release is unkown. ATP is rapid­ly hydrolyzed to adenosine, which is no longer an inactive ATP metabolite, since it modulates, through presynaptic receptors, the release of sympathetic co-transmitters. Adenosine can also be released by hypoxia. Combining electrophysiology, bioassays, cell bi­ology and analytical techniques, we investigate fundamental physiological aspects of extracellu­lar nucleotides.

• Mechanisms of extracellular nucleotide release
• The modulator role of trace metals in P2X receptor function
• P2Y receptor signaling

Selected References

Author(s)	Title	Date
Coddou C., Acuña-Castillo C., Bull P., Huidobro-Toro J.P.	Dissecting the facilitator and inhibitor allosteric metal sites of the P2X4 receptor channel: critical roles of Cys-132 for zinc-potentiation and Asp-138 for copper-inhibition. J	0
Buvinic, S., Poblete, MI., Donoso, MV:; Delpiano, AM, Briones, R., Miranda, R. & Huidobro-Toro, J.P.	P2Y1 and P2Y2 receptor distribiution varies along the human placental vascular tree: role of nucleotides in vascular tone regulation. J. Physiol (Lond), 427-443 (2006).	0
Donoso, M.V., Aedo, F. & Huidobro-Toro, J.P.	The role of adenosine A2A and A3 receptors on the differential modulation of norepinephrine and neuropeptide Y release from peripheral sympathetic nerve endings. J. Neurochem., 96:	0
Lorca, R.A., Coddou, C., Gazitúa, M.C., Bull, P. Arredondo, C., & Huidobro-Toro, J.P.	Critical role of extracellular histidines in the allosteric modulation of the P2X2 receptor by copper. 95: 499-512 J. Neurochem (2005).	0
Donoso, M.V., Miranda, R. & Huidobro-Toro, J.P.	Adenosine A2B receptors mediates human vasoconstriction and signals through the arachidonic acid cascade. Am. J. Physiol Heart Circ Physiol., 288: H2439-H2449 (2005).	0
Coddou, C., Morales, B., González, J., Grauso, M., Gordillo, F., Bull, P., Rassendren, F. & Huidobro-Toro, J.P.	Histidine 140 plays a key role in the inhibitory modulation of the P2X4 nucleotide receptors by copper but not zinc. J Biol Chem 278: 36777-36785 (2003).	0

 

Academic CV

• Biologist, PUC (1971)
• PhD, Pharmacology, UCSF (1978)
• Full Professor, Faculty of Biological Sciences, PUC
• Head Nucleotide Research Labs

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