Acta Physiologica 2010; Volume 200, Supplement 681
Abstracts of the 61st National Congress of the Italian Physiological Society
PKA AND A2A ADENOSINE RECEPTOR ACTIVATION FUNCTIONALLY MODULATE HUMAN NICOTINIC 34 RECEPTORS
Abstract number: P55
DI ANGELANTONIO1 S, PICCIONI2 A, MORICONI1 C, LIMATOLA1 C, GRASSI1 F
1Dipartimento di Fisiologia e Farmacologia,
2Dipartimento di Biologia Cellulare e dello sviluppo Sapienza Universit di Roma, Roma
We characterized here the effect of adenosine receptor A2A activation in the modulation of human neuronal nicotinic receptors, and the role played by protein kinase A activation. The modulation of a3b4 receptor properties of wild-type (wt) and sporadic amyotrophic lateral sclerosis (sALS) associated mutant nAChRs (Sabatelli et al 2009). by PKA and A2A activation was evaluated in transfected HEK cells by patch clamp recordings.
PKA activation either by intracellular dialysis with PKA catalytic subunit, or by extracellular application of 8-Br-cAMP, in transfected HEK cells with wt a3b4 induced: i) an increase of the apparent affinity in the dose response relationship for nicotine; ii) a reduced use-dependent rundown of both ACh and nicotine evoked currents; and iii) a faster recovery from use-dependent current rundown.
On HEK cells co-transfected wt a3b4 nAChRs and A2AR, tonic activation of A2AR by basal adenosine reduced nAChR current rundown. This effect was prevented by adenosine deaminase or SCH58261 (A2AR antagonist) treatment. All these effects were absent in sALS associated mutant receptors in which a consensus site for protein kinases was missed.
Sabatelli M et al., 2009 Hum Mol Genet., 18(20):39974006
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Acta Physiologica 2010; Volume 200, Supplement 681 :P55