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On the suitability of adenosine 3'-phosphate 5'-phosphosulphate as a selective P2Y receptor antagonist in intact tissues. 1998

R Bültmann, and F Tuluc, and K Starke
Pharmakologisches Institut, Freiburg i. Br., Germany.

Agonist and antagonist effects of the putative P2Y1 receptor antagonist adenosine 3'-phosphate 5'-phosphosulphate (PAPS) were studied in intact tissues. In the carbachol-precontracted guinea-pig taenia coli, PAPS caused prominent relaxation (EC50 3.3 microM). The response was attenuated by the P2 receptor antagonists 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS) and reactive red 2 with apparent Kd values (0.27 and 0.29 microM) indicating that PAPS acts through the non-P2Y receptor, which is the site of action of alpha,beta-methylene ATP (alpha,beta-MeATP) in the taenia coli. Incubation with PAPS (10-100 microM) attenuated the P2Y receptor-mediated relaxation caused by 5'-O-(2-thiodiphosphate) (ADPbetaS); PAPS (100 microM) also attenuated the relaxation caused by alpha,beta-MeATP, as well as the alpha1-adrenoceptor-mediated response to noradrenaline. In the noradrenaline-precontracted rat aorta, PAPS caused minor relaxation (EC50 24.7 microM), which was reduced by the P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS; 1 microM), indicating that PAPS activates endothelial P2Y receptors. Incubation with PAPS (10 and 100 microM) attenuated the P2Y receptor-mediated relaxation caused by ADPbetaS; PAPS (100 microM) also attenuated the P2U receptor-mediated relaxation caused by UTP and the muscarine receptor-mediated response to acetylcholine. In rat vas deferens, PAPS (100 microM) attenuated the P2X receptor-mediated contraction elicited by alpha,beta-MeATP but did not alter the alpha1-adrenoceptor-mediated response to noradrenaline. The results indicate that PAPS attenuates P2Y receptor-mediated relaxation in intact tissues. However, due to its limited subtype selectivity and non-P2 receptor effects, the nucleotide is not a suitable antagonist for this subtype.

UI MeSH Term Description Entries
D008297 Male Males
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D010724 Phosphoadenosine Phosphosulfate 3'-Phosphoadenosine-5'-phosphosulfate. Key intermediate in the formation by living cells of sulfate esters of phenols, alcohols, steroids, sulfated polysaccharides, and simple esters, such as choline sulfate. It is formed from sulfate ion and ATP in a two-step process. This compound also is an important step in the process of sulfur fixation in plants and microorganisms. Adenosine-3'-phosphate-5'-Phosphosulfate,Adenosine 3' phosphate 5' Phosphosulfate,Phosphosulfate, Phosphoadenosine
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001011 Aorta The main trunk of the systemic arteries. Aortas
D014649 Vas Deferens The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct. Ductus Deferens,Deferens, Ductus,Deferens, Vas
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D058472 Receptors, Purinergic P2Y1 A subclass of purinergic P2Y receptors that have a preference for ATP and ADP. The activated P2Y1 receptor signals through the G-PROTEIN-coupled activation of PHOSPHOLIPASE C and mobilization of intracellular CALCIUM. P2Y1 Purinoceptor,P2Y1 Purinoceptors,P2Y1 Receptor,P2Y1 Receptors,Purinergic Receptor P2Y, G-Protein Coupled, 1,Purinoceptor P2Y1,P2Y1 Receptors, Purinergic,Purinergic P2Y1 Receptors,Purinoceptor, P2Y1,Purinoceptors, P2Y1,Receptor, P2Y1,Receptors, P2Y1

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