THE STEREOSELECTIVE O-METHYLATION OF ISOPRENALINE IN THE ISOLATED RABBIT THORACIC AORTA

This investigation examined the stereoselective nature of the steroid-sensitive extraneuronal O-methylation process for the isomers of isoprenaline in the rabbit aorta. The rate of O-methylation of (-)- and (+)-isoprenaline was linear with substrate concentration in the range 0.24 to 4.7 .mu.mol .cntdot. l-1. There was marked preference for the O-methylation of (-)-isoprenaline rather than (+)-isoprenaline at low (< 0.94 .mu.mol .cntdot. l-1) substrate concentrations. In contrast, at concentrations .gtoreq. 9.4 .mu.mol .cntdot. l-1 the rates of O-methylation of (-)- and (+)-isoprenaline were similar. Phenoxybenzamine (30 .mu.mol .cntdot. l-1) inhibited but did not abolish the O-methylation of both (-)- and (+)-isoprenaline when the isomers were present in a concentration range of 0.24 .mu.mol .cntdot. l-1 to 9.4 .mu.mol .cntdot. l-1. Phenoxybenzamine did not significantly influence the O-methylation of either (-)- or (+)-isoprenaline when the isomers were present at a concentration of 24 .mu.mol .cntdot. l-1. Deoxycorticosterone acetate (DOCA) produced an equipotent and marked inhibition of the O-methylation of both (-)- and (+)-isoprenaline at a low (0.24 .mu.mol .cntdot. l-1) substrate concentration. When higher substrate concentrations were used, there was a significantly greater resistance to the inhibition of O-methylation of (-)-isoprenaline than was the case for (+)-isoprenaline. At a concentration of 9.4 .mu.mol .cntdot. l-1, the steroid failed to inhibit the O-methylation of (-)-isoprenaline but was effective in inhibiting the O-methylation of (+)-isoprenaline. The selective inhibitory influence of DOCA on the O-methylation of (+)-isoprenaline was unaltered in cocaine-treated tissues and in tissues incubated with propranolol. The latter observations suggest that neuronal uptake mechanisms and beta adrenoceptor mediated processes were not involved in the selective actions of DOCA upon the (+)-isomer of isoprenaline. Phenoxybenzamine- and steroid-sensitive extraneuronal O-methylation of isoprenaline is stereoselective. Moreover the resistance of O-methylation to phenoxybenzamine and DOCA particularly at high substrate concentrations is due to non-stereoselective diffusional entry of isoprenaline to a site or sites of O-methylation.