The receptors concerned in the actions of catecholamines on glucose release, membrane potential and ion movements in guinea-pig liver.

1. Experiments have been made to identify the kinds of receptors concerned in the actions of catecholamines in increasing potassium efflux, membrane potential and glucose release in tissue slices prepared from guinea-pig liver.2. Glucose release could be accelerated by activation of either of two distinct receptors, one of which resembles the alpha receptor of Ahlquist's classification, the other being beta-like. Thus both amidephrine and isoprenaline (sympathomimetic amines which selectively activate alpha and beta receptors respectively) elicited the response.3. The effect of isoprenaline on glucose release was inhibited by the beta blocking agent propranolol (1 muM) but not by the alpha blocker phentolamine (10 muM), whereas the converse held for amidephrine. However, the degree of antagonism observed with phentolamine was less than found in smooth muscle, suggesting that the alpha-like receptor in the liver may differ somewhat from that in other tissues, or be less accessible to the antagonist.4. Amidephrine, like noradrenaline, increased the efflux of (42)K from the slices and caused hyperpolarization, suggesting that the increase in potassium permeability underlying these responses is alpha-mediated. This conclusion was supported by the finding that the effect of amidephrine on membrane potential was inhibited by phentolamine but not propranolol (1 muM).5. In keeping with this interpretation, low concentrations (20-50 nM) of isoprenaline, although sufficient to activate the beta receptors (as judged by the effect on glucose release) had little effect on the ionic composition of the tissue, and caused only a small increase in (42)K efflux. Thus the ;ion movement' and ;glucose' responses could be largely dissociated.6. Larger concentrations (1-6 muM) of isoprenaline increased (42)K efflux to a greater extent, although the effect was always less than with the same concentration of noradrenaline.7. Activation of the beta-receptors caused a small and inconsistent hyperpolarization which became more pronounced and also more reproducible on replacing the chloride content of the bathing fluid by the larger anion isethionate.8. Although these results show that activation of either of two distinct adrenergic receptors in guinea-pig liver can cause the same end-response (e.g. an increase in glucose release, or, under some circumstances, hyperpolarization of the cell membrane), the underlying mechanisms cannot be assumed to be identical. This is discussed.