Pre- and postjunctional actions of purine and xanthine compounds in the guinea-pig caecum circular muscle.

1. The sucrose-gap technique was used to study pre- and postjunctional actions of P1-purinoceptor and P2-purinoceptor agonists and a range of xanthine derivatives in the guinea-pig caecum circular muscle. 2. Adenosine, 2-chloroadenosine (2-ClAd), ATP and alpha,beta-methylene ATP all caused concentration-dependent hyperpolarization of the smooth muscle membrane with a rank order of potency of 2-ClAd greater than alpha,beta-methylene ATP greater than adenosine. 3. The xanthine derivatives caffeine, theophylline, 8-phenyltheophylline and 1,3-dipropyl-8-(2-amino-4-chlorophenyl) xanthine (PACPX) at submicromolar concentrations evoked depolarization of the smooth muscle membrane. At higher concentrations, all these compounds and enprofylline caused concentration-dependent hyperpolarization. 4. All the purine compounds tested caused a reduction in the amplitude of the non-adrenergic, non-cholinergic inhibitory junction potential (i.j.p.). For the P1-purinoceptor agonists adenosine and 2-ClAd this was almost entirely a prejunctional effect. For the P2-purinoceptor agonists this was mostly a postjunctional effect because both ATP and alpha,beta-methylene ATP caused significantly greater increases in the conductance of the smooth muscle membrane than did adenosine or 2-ClAd. 5. All the xanthine compounds tested (up to 100 microM), except enprofylline, were capable of increasing the amplitude of the i.j.p. At millimolar concentrations both caffeine and theophylline could reduce the i.j.p. amplitude. 6. It is concluded that there are inhibitory prejunctional P1-purinoceptors on the i.j.p.-producing neurones in the guinea-pig caecum circular muscle and that, of the xanthine derivatives tested, none of them would be suitable to use as a P1-purinoceptor antagonist in this preparation because of their own direct effects.