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Activation of P 1 ‐ and P 2Y ‐purinoceptors by ADP‐ribose in the guinea‐pig taenia coli, but not of P 2X ‐purinoceptors in the vas deferens
Author(s) -
Hoyle Charles H.V.,
Edwards Gareth A.
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.tb12753.x
Subject(s) - taenia coli , adenosine , purinergic receptor , ribose , vas deferens , adenosine triphosphate , adenosine diphosphate , purine , medicine , guinea pig , endocrinology , chemistry , adenosine monophosphate , biology , biochemistry , enzyme , platelet , platelet aggregation
1 The activity of adenosine 5′‐diphosphoribose (ADP‐ribose), a ribosylated purine nucleotide, was investigated on the carbachol‐contracted taenia coli, a tissue possessing P 1 ‐ (A 2 ) and P 2Y ‐purinoceptors and on the guinea‐pig vas deferens which possesses P 2X ‐purinoceptors. 2 In the vas deferens, where ATP (1 μ m ‐1 m m ) produced concentration‐dependent contractions, ADP‐ribose was without effect at concentrations up to 1 m m . 3 In the taenia coli, ADP‐ribose (0.1 μ m ‐1 m m ) produced concentration‐dependent relaxations with a potency similar to that of adenosine, but less than that of ATP. The pD 2 values for ADP‐ribose, adenosine and ATP were 4.5 ± 0.07 (27), 4.4 ± 0.10 (9) and 5.5 ± 0.14 (21), respectively. The time‐course of the relaxations elicited by ADP‐ribose was found to be significantly longer than that for ATP and significantly shorter than that for adenosine. 4 The P 1 ‐purinoceptor antagonist, 8‐phenyltheophylline (5 μ m ), produced parallel rightward shifts in the concentration‐response curves of the relaxations of the taenia coli elicited by ADP‐ribose and adenosine but not ATP. 5 Dipyridamole (0.3 μ m ), a purine nucleoside uptake inhibitor, potentiated the responses to adenosine and ADP‐ribose in the taenia coli. These potentiations were sensitive to 8‐phenyltheophylline (5 μ m ). 6 Reactive blue 2, a P 2Y ‐purinoceptor antagonist, antagonized the inhibitory responses of ADP‐ribose and ATP in the taenia coli, without significantly altering the inhibitory responses of either adenosine or noradrenaline. 7 In the presence of the potassium channel blocker, apamin (0.3 μ m ), the inhibitory responses of ADP‐ribose were severely attenuated, and the inhibitory responses of ATP in the taenia coli were converted to transient contractions. Further addition of 8‐PT blocked the residual responses of ADP‐ribose. 8 The P 2 ‐purinoceptor antagonist, suramin (500 μ m ), antagonized responses to ATP and ADP‐ribose, but not adenosine. Further addition of 8‐PT antagonized the residual responses to ADP‐ribose, but not to ATP. 9 It is concluded that ADP‐ribose has a mixed pharmacological profile, evoking both P 1 (A 2 )‐purinoceptor‐mediated responses and P 2Y ‐purinoceptor‐mediated responses, while being inert at P 2X ‐purinoceptors. It is suggested that ADP‐ribose may provide a useful starting point for the generation of structural analogues which have specific activity at the P 2Y ‐purinoceptor.