INTERACTIONS BETWEEN THE EFFECTS OF α‐ AND β‐ADRENOCEPTOR AGONISTS AND ADENINE NUCLEOTIDES ON THE MEMBRANE POTENTIAL OF CELLS IN GUINEA‐PIG LIVER SLICES

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Abstract
1 The β-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 α-agonists. However, after a selective α-adrenoceptor agonist has been applied, the response to isoprenaline becomes greatly enhanced. 2 Simultaneous application of small doses of an α- and a β-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 α-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 α-agonist. However, ADP and ATP are themselves able to enhance the response to β-agonists. 6 These interactions between α-agonists, β-agonists and adenine nucleotides seem to involve steps subsequent to receptor activation. Changes in the intracellular actions of cyclic AMP may be concerned.

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