BRAIN MATURATION OF HIGH-AFFINITY ADENOSINE A(2) RECEPTORS AND THEIR COUPLING TO G-PROTEINS

The neuromodulator adenosine is acting through specific receptors, A(1 ) and A(2), coupled to their effector systems via G-proteins. The regu latory effects of adenosine on locomotor activity have been attributed to an interaction with A(2) striatal receptors. The postnatal develop ment of adenosine A(2a) receptors was analysed in rat striatal membran es and by quantitative autoradiography in brain sections using [H-3]CG S 21680 as specific probe. At the concentration of radioligand used (5 nM), A(2a) sites were concentrated in the striatum at all ages, with minor developmental alterations in the expression pattern within the s triatal regions. In membrane preparations, Scatchard analysis showed t hat the density of CGS 21680 binding sites was low at birth, around 3% of the adult value, and then increased, mostly between birth and 5 da ys and then from 15 days to adulthood. Concomitantly, the receptor aff inity decreased sharply during brain development, K-d values varying f rom 2 to 15.5 nM. The addition of a GTP analogue, guanylyl-5'-imidodip hosphate (Gpp(NH)p, 10 mu M), to the assay medium reduced significantl y the receptor affinity throughout the postnatal development, reflecti ng a coupling to G-proteins at all ages, but it also suggested a weake r association at birth. These data show that the developmental propert ies of A(2a) receptors contrast with those of A(1) receptors, and emph asize the role played by adenosine through its A(2) receptors in the m aturation of striatum-related cerebral pathways.