DOES TETRAHYDROPAPAVEROLINE CONTRIBUTE TO CARDIOVASCULAR ACTIONS OF DOPAMINE

It has been previously shown in vitro that dopamine (DA) in the presence of monoamine oxidase condenses with its corresponding aldehyde (dihydroxyphenylacetaldehyde) to yield tetrahydropapaveroline (THP), an isoquinoline derivative structurally related to papaverine, which exhibits β-adrenergic activity. A sensitive method has been developed for the extraction and separation of dopamine-2-14C (DA-2-14C) and its metabolites by using thin-layer chromatography and liquid scintillation counting. At 2 and 5 min after the i.v. injection of 250 μ/kg of DA-2-14C, samples of several guinea pig tissues were analyzed for THP-14C. With the exception of the liver, no tissue contained any amount of THP greater than that seen in samples which served as controls for nonenzymatic conversion of DA to THP-like materials during the course of the extraction procedure. An explanation of the failure to detect significant amounts of THP in vivo was found when varying concentrations of DA were incubated with guinea pig liver mitochondria. When 1 mg/ml of DA-2-14C was incubated, approximately 15 per cent of the radioactivity was converted to THP in 5 min, while the major metabolite was dihydroxyphenylacetic acid. Incubation in vitro of 0.24 mg/ml of DA-2-14C, which more closely approximates the level of DA in vivo after the injection of the above dose, resulted in a conversion of only 3 per cent of the DA to THP. It was concluded that the cardiovascular responses seen with DA are not mediated by THP, since at most only trace amounts were detected. Based on the potency of THP, these amounts are considerably below the quantities of THP necessary to produce the depressor response. © 1968.