CONTRACTION OF THE RAT ISOLATED SPLEEN MEDIATED BY ADENOSINE-A1-RECEPTOR ACTIVATION

1 A series of adenosine receptor agonists of varying degrees of select ivity induced concentration-dependent contraction of the rat isolated spleen. With the exception of the response to the selective A2A recept or agonist, l)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21 680), responses to each ligand were blocked surmountably and to a broa dly similar extent by 8-p-sulphophenyltheophylline (10(-5) M). 2 There was a significant correlation between the pEC50 values obtained on th e spleen and the binding affinities (pK(D); measured with [H-3]-NECA) for the A1 receptor of pig striatum (r = 0.98, P<0.001) but not the A2 A receptor (r = 0. 14, NS). 3 The antagonist potencies of 1,3-dipropyl -8-cyclopentylxanthine (DPCPX) and 9-chloro-2-furyl [1,2,3]triazolo[1, 5-C]quinazoline-5-amine (CGS 15943) were measured against the prototyp e selective A1 receptor agonist, R-N6-phenylisopropyladenosine (R-PIA) . The resulting pK(B) values of 8.67 and 7.70, respectively are consis tent with the A1 receptor subtype mediating splenic contraction. 4 The response to R-PIA was unaltered in the presence of a concentration (1 0(-7) M) of CGS 21680 which is 6 fold its K(D) concentration at the A2 A binding site in pig striatum but below the threshold for causing con traction per se; thus, A2A receptors inhibitory to contraction appear to be absent. 5 The response to R-PIA was resistant to blockade by pra zosin (10(-7) M) and by nifedipine (10(-6) m) but partially blocked by indomethacin (10(-6) M). 6 The results show that the rat isolated spl een responds to adenosine receptor agonists with contraction. Both the relative potencies of agonists and the effects of antagonists indicat e mediation by the A1 receptor subtype. Alpha1-Adrenoceptor activation is not involved in contraction but a role for products of cyclo-oxyge nase and calcium from a source not dependent on entry through L-channe ls is implicated.