Evidence for an increased catecholamine synthesis in rat adrenal glands following stimulation of peripheral dopamine receptors.
In studies on peripheral dopamine (DA) turnover in our department evidence has accumulated that changes in adrenal DA levels induced by varying degrees of neurogenic stimulation roughly reflect changes in the catecholamine (CA) synthesis rate. The question arises if changes in DA levels in rat adrenals induced by different DA D-2 receptor agonists and previously reported from our laboratory, also indicate changes in CA synthesis. After various periods of drug administration rats were killed by decapitation and tissue CA levels in adrenals and forebrain were determined by HPLC-EC. The potent inhibitor of DA-beta-hydroxylase FLA 63 (40 mg/kg i.p.) increased adrenal DA by 186% after 1 h and by 423% after 3 h. The DA D-2 agonist quinpirole (0.2 mg/kg s.c., 30 min) itself increased adrenal DA by 55-60% compared to control. In FLA 63 pretreated rats quinpirole increased adrenal DA levels by further 127% (FLA 63-1 h), resp. 122% (FLA 63-3 h) than did FLA 63 itself. The DA D-2 receptor antagonist domperidone (3 mg/kg s.c., 150 min) blocked the quinpirole effect both in saline and FLA 63 (3 h) pretreated rats. Adrenal DOPAC was changed in similar manner as adrenal DA in FLA 63 pretreated rats. No significant changes either in adrenal NA or A were observed after FLA 63 pretreatment. Under the present experimental conditions adrenal DA may thus mainly be looked upon as an intermediate in the synthesis of NA and A, and the elevation of DA induced by DA D-2 receptor stimulation as a consequence of increased catecholamine synthesis.
Kujacic
M
M
Department of Pharmacology, University of Göteborg, Sweden.
Carlsson
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis; D015259:Dopamine Agents / Q000494:pharmacology*; D004563:Electrochemistry; D004837:Epinephrine / Q000096:biosynthesis; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013268:Stimulation, Chemical
D002395:Catecholamines; D015259:Dopamine Agents; D004873:Ergolines; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D004294:Domperidone; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine