Rawlow A, Fleig H, Kurahashi K, Trendelenburg U
Naunyn Schmiedebergs Arch Pharmacol. 1980 Nov;314(3):237-47. doi: 10.1007/BF00498545.
The neuronal and extraneuronal uptake and deamination of 3H-(-)-phenylephrine was studied in perfused rat hearts obtained from reserpine-pretreated animals. 1. Under the conditions of steady-state perfusion with 5 mumol/l 3H-(-)-phenylephrine slightly more than 50% of total deamination took place in adrenergic nerve endings, slightly less than 50% in the extraneuronal tissue. 2. 3H-(-)-phenylephrine is preferentially deaminated to the glycol metabolite. 3. There is pronounced non-saturable, cocaine- and corticosterone-resistant uptake of 3H-(-)-phenylephrine in the perfused rat heart. 4. The apparent rate constants for the efflux of the glycol metabolite is about 20 times higher than that for the efflux of the acid metabolite. 5. For both the glycol and the acid metabolite of 3H-(-)-phenylephrine, apparent rate constants for the efflux declined when the duration of the perfusion with the labelled parent amine was prolonged. This phenomenon was also observed when the deamination of 3H-(-)-phenylephrine was restricted to either the adrenergic nerve endings or the extraneuronal tissue. These results are interpreted as evidence for a distribution of each metabolite into at least two kinetically different compartments. 6. This was confirmed for the acid metabolite by determination of a biphasic efflux curve in wash-out experiments in which MAO was inhibited during wash-out (after an initial loading of the adrenergic nerve endings with 3H-(-)-phenylephrine).
