Dihydroxyphenylalanine and Dopamine Are Released from Portal Vein Together with Noradrenaline and Dihydroxyphenylglycol During Nerve Stimulation

Abstract

The overflows of 3,4-dihydroxyphenylalanine, dopamine, noradrenaline, and 3,4-dihydroxyphenylglycol in canine portal vein superfused in vitro were studied before, during, and after depolarization of sympathetic nerve endings. The four compounds were separated from superfusate and from tissue on Sep-Pak C-18 cartridges and quantified by HPLC with electrochemical detection. Physiological and biochemical methods were used to show that the compound released was most probably 3,4-dihydroxyphenylalanine; the identity of the other endogenous compounds has been established previously. Release of 3,4-dihydroxyphenylalanine was calcium and frequency dependent, inhibited by a-m-L-p-tyrosine (an inhibitor of tyrosine hydroxylase) and augmented by 3-hydroxybenzylhydrazine (an inhibitor of aromatic amino acid decarboxylase). The overflows of dopamine, noradrenaline, and 3,4-dihydroxyphenylglycol from the vein were calcium and frequency dependent. It was estimated that under control conditions, approximately 80% of the total 3,4-dihydroxyphenylalanine that was synthesized was directed to catecholamine biosynthesis, approximately 8% overflowed from the vein, and approximately 14% remained unchanged within the tissue. It is concluded that 3,4-dihydroxyphenylalanine and dopamine are released together with noradrenaline and 3,4-dihydroxyphenylglycol from portal vein upon nerve depolarization.

Increase in plasma 3,4‐dihydroxyphenylalanine (DOPA) appearance rate after inhibition of DOPA decarboxylase in humans

“…Tyrosine hydroxylase is principally confined to catecholamine-producing tissues [ 13. A number of findings do not, however, support this theory: ( I ) There is no depot of DOPA in sympathetic nerves or alternatively it is very small as compared to amounts of DOPA in muscles [3]; (2) There is clearly no close relationship between sympathetic activity as determined by plasma norepinephrine and plasma DOPA [2, 4, 5, 61; (3) In vitro studies have demonstrated a very small DOPA overflow as compared to the norepinephrine overflow whereas DOPA concentrations in plasma are much higher than those of norepinephrine [7]. Some authors have concluded, that plasma DOPA levels appear to reflect the rate of tyrosine hydroxylation throughout the body, including to some extent brain (for review see [2]).…”

Effluxes of 3,4‐Dihydroxyphenylalanine, 3,4‐Dihydroxyphenylglycol, and Norepinephrine from Four Blood Vessels During Basal Conditions and During Nerve Stimulation

“…J. Neurochem. 64,833-841 (1995) .3,4-Dihydroxyphenylanine (DOPA) overflows from isolated superfused segments of canine portal vein together with norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DHPG) (Hunter et al, 1992) . The overflow of DOPA is increased in a frequency-dependent manner by nerve stimulation .…”

“…DOPA is a pivotal com-833 pound in the synthesis of NE because it is the product of tyrosine hydroxylation, the rate-limiting reaction in catecholamine synthesis (Levitt et al ., 1965) . In the portal vein we showed that when tyrosine hydroxylase (TH) was inhibited, DOPA efflux was greatly attenuated (Hunter et al ., 1992), and when TH activity was increased as a result of nerve stimulation (Alousi and Weiner, 1966), DOPA efflux was increased . Thus, we proposed that quantification of DOPA in superfusates could be useful as an index of TH activity (Hunter et al ., 1992) .In the present study we initially measured the effluxes of DOPA, NE, and DHPG from four different isolated blood vessels of the dog : saphenous and portal veins and pulmonary and mesenteric arteries .…”

“…In the portal vein we showed that when tyrosine hydroxylase (TH) was inhibited, DOPA efflux was greatly attenuated (Hunter et al ., 1992), and when TH activity was increased as a result of nerve stimulation (Alousi and Weiner, 1966), DOPA efflux was increased . Thus, we proposed that quantification of DOPA in superfusates could be useful as an index of TH activity (Hunter et al ., 1992) .In the present study we initially measured the effluxes of DOPA, NE, and DHPG from four different isolated blood vessels of the dog : saphenous and portal veins and pulmonary and mesenteric arteries . Clear differences became apparent in the amounts of these catechols effluxing from different vessels under the same experimental conditions, and we questioned whether these differences were related to dissimilarities between vessels in the content of catecholamines in tissue, the synthesis of catecholamines, the retention of NE in storage vesicles, or the release and the reuptake of NE .…”

L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor

“…This observation was correlated with the change in blood pressure during the dark-active phase monitored by the tail cuff method ( Figure 7F). Because L-DOPA is an endogenous ligand for GPR143 and is released from sympathetic neurons and adrenal medullae in an activity-dependent manner (3)(4)(5)33), it is possible that the disruption in day and night blood pressure variation in Gpr143 -/y mice might be due to dysfunction of the sympathetic nervous system. To examine possible involvement of sympathetic activity, we measured plasma levels of L-DOPA, noradrenaline (NA), and adrenaline (Ad) in these mice during light and dark phases.…”