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 mumol X 1(-1). There was marked preference for the O-methylation of (-)-isoprenaline rather than (+)-isoprenaline at low (less than 0.94 mumol X 1(-1) substrate concentrations. In contrast, at concentrations equal to or greater than 9.4 mumol X 1(-1) the rates of O-methylation of (-)- and (+)-isoprenaline were similar. Phenoxybenzamine (30 mumol X 1(-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 mumol X 1(-1) to 9.4 mumol X 1(-1). Phenoxybenzamine did not significantly influence the O-methylation of either (-)- or (+)-isoprenaline when the isomers were present at a concentration of 24 mumol X 1(-1). Deoxycorticosterone acetate (DOCA) produced an equipotent and marked inhibition of the O-methylation of both (-)- and (+)-isoprenaline at a low (0.24 mumol X 1(-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 mumol X 1(-1), the steroid failed to inhibit the O-methylation of (-)-isoprenaline but was effective in inhibiting the O-methylation of (+)-isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002851:Chromatography, High Pressure Liquid; D003900:Desoxycorticosterone / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008745:Methylation; D009474:Neurons / Q000378:metabolism; D009647:Normetanephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D013237:Stereoisomerism
D065098:Catechol O-Methyltransferase Inhibitors; D009647:Normetanephrine; D010643:Phenoxybenzamine; D003900:Desoxycorticosterone; D011433:Propranolol; D002394:Catechol O-Methyltransferase; D007545:Isoproterenol