Determination of differential activities of soluble and membrane-bound catechol-O-methyltransferase in tissues and erythrocytes.

Catechol-O-methyltransferase (COMT) exists as two isoenzymes, a membrane-bound form (MB-COMT) and a soluble form (S-COMT), with different roles in the metabolism of catecholamines and other catechol compounds. This report documents an HPLC assay for separate estimation of S-COMT and MB-COMT activity and examines activities of the two isoenzymes among different rat tissues and in human and rat erythrocytes. Activities of MB-COMT and S-COMT varied widely among tissues. There were higher activities of S-COMT than MB-COMT in all tissues except the adrenal medulla where MB-COMT was the predominant isoenzyme, consistent with the importance of this tissue and MB-COMT for the O-methylation of catecholamines. MB-COMT and S-COMT in rat and human erythrocytes showed divergent levels and patterns of activity. The assay represents a rapid and accurate method for quantifying MB-COMT and S-COMT in various tissues and examining the relative roles of COMT isoenzymes in the metabolism of catechol compounds in health and disease.