Agonist and antagonist characterization of the P2-purinoceptors in the guinea pig ileum

Abstract

When adenine nucleotides were administered to isolated guinea pig ileum longitudinal muscle, two immediate effects were observed: a contractile effect and a concomitant inhibition of the responses elicited by transmural nerve stimulation. At concentrations up to 10(-4) M the order of potency for the contractile effect was alpha,beta-MeADP = alpha,beta-MeATP greater than ADP = ATP = AMPPNP = beta, tau-MeATP greater than 2'-deoxy AMP = 2'-deoxy ADP. AMP and adenosine did not show any contractile effect, whereas both compounds dose-dependently and reversibly inhibited the nerve-induced contractile responses. ADP, ATP, beta,tau-MeATP and AMPPNP also inhibited contractile responses to transmural nerve stimulation, whereas 2'-deoxy AMP, 2'-deoxy ADP, alpha,beta-MeADP and alpha,beta-MeATP showed but weak inhibitory effects, 2'-deoxyadenosine, IMP, IDP, ITP, 8-BrATP and TDP lacked significant contractile effects and did not exert a significant inhibition on nerve-induced contractions. p-chloromercuribenzene sulphonic acid (PCMBS) irreversibly antagonized the contractile effects of ADP, ATP and the alpha,beta-methylene derivatives, whereas dantrolene sodium, tetrodotoxin, scopolamine and 8-p-sulphophenyltheophylline were without effect on nucleotide-induced contractions. The contractile effect of ADP or ATP was unaffected by indomethacin, whereas the contractile effect by alpha,beta-methylene derivatives was abolished by indomethacin. ADP, ATP and alpha,beta-MeADP enhanced contractile responses to exogenous acetylcholine, alpha,beta-MeADP being most effective. This enhancement was blocked by indomethacin. We suggest that ADP and ATP contracted the guinea pig ileum by an action at postjunctional P2-purinoceptors with different characteristics from prejunctional P1-purinoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)