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.