Contraction of the rat isolated spleen mediated by adenosine A1 receptor activation

Abstract

1. A series of adenosine receptor agonists of varying degrees of selectivity induced concentration-dependent contraction of the rat isolated spleen. With the exception of the response to the selective A2A receptor agonist, 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N- ethylcarboxamidoadenosine (CGS 21680), responses to each ligand were blocked surmountably and to a broadly similar extent by 8-p-sulphophenyltheophylline (10(-5) M). 2. There was a significant correlation between the pEC50 values obtained on the spleen and the binding affinities (pKD; measured with [3H]-NECA) for the A1 receptor of pig striatum (r = 0.98, P < 0.001) but not the A2A 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 prototype selective A1 receptor agonist, R-N6-phenylisopropyladenosine (R-PIA). The resulting pKB values of 8.67 and 7.70, respectively are consistent with the A1 receptor subtype mediating splenic contraction. 4. The response to R-PIA was unaltered in the presence of a concentration (10(-7) M) of CGS 21680 which is 6 fold its KD concentration at the A2A binding site in pig striatum but below the threshold for causing contraction per se; thus, A2A receptors inhibitory to contraction appear to be absent. 5. The response to R-PIA was resistant to blockade by prazosin (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 spleen responds to adenosine receptor agonists with contraction. Both the relative potencies of agonists and the effects of antagonists indicate mediation by the A1 receptor subtype. alpha1-Adrenoceptor activation is not involved in contraction but a role for products of cyclo-oxygenase and calcium from a source not dependent on entry through L-channels is implicated.