Interactions between the effects of alpha- and beta-adrenoceptor agonists and adenine nucleotides on the membrane potential of cells in guinea-pig liver slices.

1 The beta-adrenoceptor agonist isoprenaline normally causes only a small and inconsistent increase in the membrane potential of cells in guinea-pig liver slices, in contrast to the large hyperpolarizations seen with alpha-agonists. However, after a selective alpha-adrenoceptor agonist has been applied, the response to isoprenaline becomes greatly enhanced. 2 Simultaneous application of small doses of an alpha- and beta-agonist produce hyperpolarizations larger than the sum of the responses to each agent alone. 3 These interactions occur with a range of sympathomimetic amines, including some which are not substrates for various processes for the uptake and inactivation of catecholamines. 4 Hyperpolarizations caused by externally applied cyclic adenosine-3',5'-monophosphate (cyclic AMP) also become larger after application of an alpha-agonist. 5 The adenine nucleotides adenosine 5'-diphosphate (ADP) and adenosine 5'-triphosphate (ATP) hyperpolarize guinea-pig liver cells in the dose range 0.1-1.0 mM. This response is not increased after an alpha-agonist. However, ADP and ATP are themselves able to enhance the response to beta-agonists. 6 These interactions between alpha-agonists, beta-agonists and adenine nucleotides seem to involve steps subsequent to receptor activation. Changes in the intracellular actions of cyclic AMP may be concerned.