IDENTIFICATION OF SUBSTANCE-P METABOLITES USING A COMBINATION OF REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND CAPILLARY-ELECTROPHORESIS

Gradient elution reversed-phase high-performance liquid chromatographi c and capillary electrophoretic separations were optimised to separate substance P (SP) and twelve of its fragments. The methods were applie d to a study of the in vivo metabolism of substance P in the rat after intrastriatal injection of the peptide (10 nmol). SP and significant amounts of its N-terminal fragments, SP(1-7) and SP(1-4), were detecte d but no major C-terminal fragments could be identified. At the concen tration studied, the metabolism of SP was shown to follow zero order e limination kinetics with a rate of decay of 0.2 nmol/min. As we have s hown that SP(1-4) and SP(1-7) can be produced in vivo in the striatum in relatively large amounts, it is conceivable that these fragments co ntribute to the overall pharmacological pattern of activity of the par ent peptide. (C) 1998 Elsevier Science B.V. All rights reserved.