Premium
A comparison of A 2 adenosine receptor‐induced cyclic AMP generation in cerebral cortex and relaxation of pre‐contracted aorta
Author(s) -
Alexander Stephen P.H.,
Losinski Amanda,
Kendall David A.,
Hill Stephen J.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14042.x
Subject(s) - adenosine , xanthine , cgs 21680 , adenosine receptor , adenosine a1 receptor , phenylephrine , medicine , endocrinology , chemistry , agonist , receptor , biology , biochemistry , blood pressure , enzyme
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 [ 3 H]‐cyclic AMP accumulation in [ 3 H]‐adenine‐prelabelled guinea‐pig cerebral cortical slices was stimulated by adenosine and its analogues with the following EC 50 values (μ m ): 5′‐N‐ethylcarbox‐amidoadenosine (3.1 ± 0.3) > 2‐chloroadenosine (10 ± 2) > adenosine (109 ± 15). 3 2‐Chloroadenosine and adenosine elicited maximal responses for [ 3 H]‐cyclic AMP accumulation that were 100 ± 7 and 71 ± 6% of the maximal response to 5′‐N‐ethylcarboxamidoadenosine, respectively. CGS 21680 (100 μ m ) and DPMA (100 μ m ) elicited −2 ± 2 and 12 ± 3% of the response to 100 μ 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 μ m ). 5 Adenosine analogues produced long‐lasting relaxation of phenylephrine‐precontracted aortic rings with the following rank order of potency (EC 50 values, μ 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 μ m elicited smaller relaxations of the precontracted tissues (12 ± 2 and 43 ± 15%, respectively). 6 Antagonism by xanthine derivatives of the 5′‐N‐ethylcarboxamidoadenosine‐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.