Can ATP stimulate P1-receptors in guinea-pig atrium without conversion to adenosine?
The aim of this study was to determine whether ATP must be hydrolysed to adenosine in order to activate the P1-purinoceptor. Isometric contractions of electrically paced guinea-pig isolated left atria were recorded. Purines evoked negative inotropic responses that were competitively antagonised by theophylline. The order of agonist potency was 2-chloroadenosine greater than adenosine greater than beta, gamma-methylene ATP greater than ATP. Adenosine deaminase alone, or combined with 5'-nucleotidase, attenuated responses to adenosine and 5' AMP, respectively, but did not decrease those to ATP or beta, gamma-methylene ATP. Inhibition of 5'-nucleotidase did not alter responses to ATP. Dipyridamole potentiated responses to ATP both in the absence and in the presence of adenosine deaminase. Alpha, beta-methylene ATP had little agonist activity, however this was not due to its resistance to hydrolysis as the stable beta, gamma-methylene isostere of ATP was a potent agonist. These results indicate that hydrolysis of ATP to adenosine or 5' AMP is not a pre-requisite for activation of the P1-receptor in the guinea-pig atrium.
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D011983:Receptors, Purinergic; D013806:Theophylline / Q000494:pharmacology
D011955:Receptors, Drug; D011983:Receptors, Purinergic; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D013806:Theophylline; D000243:Adenosine Deaminase; D000241:Adenosine