A COMPARISON OF A(2) ADENOSINE RECEPTOR-INDUCED CYCLIC-AMP GENERATION IN CEREBRAL-CORTEX AND RELAXATION OF PRE-CONTRACTED AORTA

1 A comparative study was carried out between the adenosine receptor mediating a stimulation of cyclic AMP formation in guinea-pig cerebral cortical slices with the adenosine receptor mediating relaxation of phenylephrine precontracted guinea-pig aortic rings. 2 [H-3]-cyclic AMP accumulation in [H-3]-adenine-prelabelled guinea-pig cerebral cortical slices was stimulated by adenosine and its analogues with the following EC(50) values (mu M): 5'-N-ethylcarboxamidoadenosine (3.1 +/- 0.3)>2-chloroadenosine (10 +/- 2)>adenosine (109 +/- 15). 3 2-Chloroadenosine and adenosine elicited maximal responses for [H-3]-cyclic AMP accumulation that were 100 +/- 7 and 71 +/- 6% of the maximal response to 5'-N-ethylcarboxamido adenosine, respectively. CGS 21680 (100 mu M) and DPMA (100 mu M) elicited -2 +/- 2 and 12 +/- 3% of the response to 100 mu M 5'-N-ethylcarboxamidoadenosine. 4 Estimation of antagonist potencies at the A(2) adenosine receptor of cerebral cortex showed a rank order of potency (K-1, nM): xanthine amino congener (35 +/- 3)>8-cyclopentyl-1,3-dipropylxanthine (130 +/- 22)>PD 115,199 (407 +/- 82)>3,7-dimethyl-1-propargylxanthine (13 +/- 2 mu M). 5 Adenosine analogues produced long-lasting relaxation of phenylephrine-precontracted aortic rings with the following rank order of potency (EC(50) values, mu M): 5'-N-ethylcarboxamidoadenosine (0.68 +/- 0.06)>2-chloroadenosine (4.3 +/- 0.6)>adenosine (104 +/- 13). Maximal relaxations elicited by these agents were 71 +/- 3, 98 +/- 1, and 100 +/- 1%, respectively. CGS 21680 and DPMA at 100 mu M elicited smaller relaxations of the precontracted tissues (12 +/- 2 and 43 +/- 15%, respectively). 6 Antagonism by xanthine derivatives of the 5'-N-ethylcarboxamido adenosine-induced relaxation of aortic rings showed the following rank order of potency (K-i, nM): xanthine amino congener (17 +/- 4)>8-cyclopentyl-1,3-dipropylxanthine (171 +/- 36)>PD 115,199 (341 +/- 64)>3,7-dimethyl-1-propargylxanthine (5520 +/- 820). 7 We conclude that the A(2) adenosine receptor mediating relaxation of phenylephrine-contracted aortic rings is an A(2b) adenosine receptor which exhibits certain minor differences from the A(2b) receptor which stimulates cyclic AMP accumulation in cerebral cortical slices.