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Characterization of P 1 ‐purinoceptors on rat duodenum and urinary bladder
Author(s) -
Nicholls J.,
Hourani S.M.O.,
Kitchen I.
Publication year - 1992
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.1476-5381.1992.tb09032.x
Subject(s) - cgs 21680 , adenosine , endocrinology , medicine , adenosine receptor , adenosine a1 receptor , purinergic receptor , agonist , chemistry , p2 receptor , receptor , biology
1 The P 1 ‐purinoceptors mediating relaxation of the rat duodenum and inhibition of contraction of the rat urinary bladder were characterized by use of adenosine and its analogues 5′‐N‐ethylcarboxamidoadenosine (NECA), N 6 ‐cyclopentyladenosine (CPA) and 2‐p‐((carboxyethyl)phenethylamino)‐5′‐carboxamidoadenosine (CGS 21680), as well as the A 1 ‐selective antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX). The stable analogue of adenosine 5′‐triphosphate (ATP), adenylyl 5′‐(β,γ‐methylene)diphosphonate (AMPPCP), was also used as previous work had indicated that it has a direct action on some P 1 receptors in addition to its P 2 ‐purinoceptor activity. 2 In the rat duodenum, the order of potency of the adenosine agonists was NECA ≥ CPA > AMPPCP = adenosine > CGS 21680, and DPCPX antagonized CPA and AMPPCP at a concentration of 1 n m whereas equivalent antagonism of NECA and adenosine required a concentration of 1 μ m . This suggests the presence of a mixture of A 1 and A 2 receptors in this tissue, with CPA and AMPPCP acting on the A 1 and NECA and adenosine acting on the A 2 receptors. 3 In the rat bladder, the order of potency of the adenosine agonists for inhibition of carbachol‐induced contractions was NECA ≫ adenosine > CPA = CGS 21680, and a concentration of DPCPX of 1 μ m was required to antagonize responses to NECA and adenosine. This suggests the presence of A 2 receptors in this tissue. ATP and AMPPCP each caused contractions which were not enhanced by DPCPX (1 μ m ) which suggests that in this tissue AMPPCP was acting only via P 2 receptors and had no P 1 agonist activity. That AMPPCP was active on the A 1 receptors in the duodenum but inactive on the A 2 receptors in the bladder implies that it has selectivity for the A 1 subtype. 4 That CGS 21680, which has been reported to bind selectively to the high affinity A 2a subclass of A 2 receptors, had a very low potency on the A 2 receptors in the duodenum and in the bladder suggests that these receptors are of the low affinity A 2b subclass.