FORMATION OF A "FALSE" ADRENERGIC TRANSMITTER IN CATS PRETREATED WITH 4-METHOXY- 3,5-DIHY-DROXYPHENYLALANINE AND ITS EFFECTS ON POSTGANGLIONIC SYMPA-THETIC TRANSMISSION

¹ Department of Experimental Medicine, F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland

Pretreatment of cats with (50 mg/kg p.o. 28, 20 and 4 hr before sacrifice) 4-methoxy- 3,5-dihydroxyphenylalanine resulted in a marked depletion of norepinephrine in sympathetically innervated organs (heart, 8.3%; spleen, 7.2%; iris, 17.3%; and nictitating membrane, 19.2% of controls). The response to sympathetic nerve stimulation was diminished in the heart, the nictitating membrane and the isolated perfused spleen in which both contractile response and norepinephrine output was greatly reduced. The effect of i.v. injected norepinephrine on blood pressure and nictitating membrane did not differ significantly from that on untreated controls. The chromatographic analysis of the amines present in spleen and heart after administration of 4-methoxy-3,5-dihydroxyphenylalanine revealed the accumulation of 4-methoxy-3,5-dihydroxyphenethylamine, which was liberated as a false transmitter by sympathetic nerve stimulation. The expected -hydroxylated metabolite of 4-methoxy-3,5-dihydroxyphenethylamine could be detected neither after pretreatment with 4-methoxy-3,5-dihydroxyphenylalanine nor after injection of H³-4-methoxy-3,5- dihydroxyphenethylamine. It is concluded that the diminished response to sympathetic nerve stimulation results from a reduction of the physiologic transmitter norepinephrine available for liberation and its replacement by a less potent "false" transmitter substance.