Comparison of the uptake and O-methylation of isoprenaline by cardiac and respiratory tissues of guinea-pigs

Abstract

An attempt was made to correlate the extraneuronal uptake and O-methylation of isoprenaline in cardiac and respiratory tissues with the predominant beta-adrenoceptor subtype known to mediate the sympathetic responses of these tissues. Papillary muscles, left atria, trachealis muscles and lung parenchymal strips of guinea-pigs were incubated with [3H]isoprenaline ([3H]ISO) (0.1 microM) for 60 min. Levels of total radioactivity and of separated [3H]ISO and [3H]O-methylisoprenaline ([3H]OMI) in each tissue and of [3H]OMI in the medium were determined. U-0521 (10(-4) M) inhibited tissue O-methylation and caused an elevation of unchanged [3H]ISO in the tissues. The latter effect was attributed to the fact that the normal conversion of [3H]ISO to [3H]OMI did not occur. Metanephrine (10(-5) and 10(-4) M) did not affect tissue levels of unchanged [3H]ISO, but reduced tissue levels of [3H]OMI. Levels of [3H]OMI in tissue and medium were only slightly reduced, indicating possible extracellular sites of O-methylation. In the presence of U-0521, metanephrine (10(-4) M) reduced the accumulation of [3H]ISO, indicating that metanephrine was an inhibitor of the extraneuronal uptake of isoprenaline. It is concluded that two cellular compartments for O-methylation exist, access to one being dependent upon metanephrine-sensitive extraneuronal uptake. The extraneuronal uptake capacities of the tissues (when O-methylation was inhibited) was in the order papillary muscle less than lung = atria less than trachea. Cellular O-methylating capabilities, measured from tissue [3H]OMI, was in the order papillary muscle less than atria = trachea less than lung. These orders are discussed in relation to the beta-adrenoceptor mediating the response of each tissue and to the reported degree of sympathetic innervation.