Plasma dopa responses during stress: dependence on sympathoneural activity and tyrosine hydroxylation.
Dihydroxyphenylalanine (dopa), the precursor of all the endogenous catecholamines, circulates in plasma at a concentration higher than that of the sympathetic neurotransmitter, norepinephrine (NE). Sources of dopa in plasma and the meaning of plasma dopa levels in terms of sympathoneural function have been unclear. Plasma concentrations of dopa, the catecholamines NE, epinephrine and dopamine, the deaminated catechol metabolites dihydroxyphenylglycol and dihydroxyphenylacetic acid, and the O-methylated metabolites methoxyhydroxyphenylglycol and homovanillic acid were measured during immobilization stress in conscious rats. Animals were pretreated with chlorisondamine to block ganglionic neurotransmission or with alpha-methyl-para-tyrosine to inhibit tyrosine hydroxylation. Immobilization produced rapid, sustained increases in plasma levels of dopa, catecholamines and catecholamine metabolites. Chlorisondamine decreased base-line plasma dopa and NE levels and abolished the increases in plasma dopa and NE levels during immobilization. alpha-Methyl-para-tyrosine administration produced sustained decreases in plasma dopa levels and markedly attenuated immobilization-induced increases in plasma dopa levels. Bilateral adrenalectomy augmented base-line plasma levels of dopa and NE and augmented dopa and NE responses during immobilization. The results indicate that during immobilization stress, increased postganglionic sympathoneural outflow stimulates the synthesis of dopa in sympathetic neurones and enhances release of dopa into the circulation. The data generally support the view that changes in plasma dopa levels during stress reflect in vivo changes in the rate of catecholamine biosynthesis in sympathetic nerve terminals.
Kvetnansky
R
R
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Armando
I
I
Weise
V K
VK
Holmes
C
C
Fukuhara
K
K
Deka-Starosta
A
A
Kopin
I J
IJ
Goldstein
D S
DS
D000315:Adrenalectomy; D000818:Animals; D002395:Catecholamines / Q000097:blood*; D002714:Chlorisondamine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000097:blood*; D006900:Hydroxylation; D007103:Immobilization / Q000502:physiology*; D007274:Injections, Intraperitoneal; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000097:blood*; D014443:Tyrosine / Q000378:metabolism*
D002395:Catecholamines; D008781:Methyltyrosines; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D002714:Chlorisondamine