In vivo activity of tyrosine hydroxylase in rat adrenal glands following administration of quinpirole and dopamine.
Using adrenal dopamine as indicator we have previously obtained evidence that quinpirole and several other agonists on dopamine D2-like receptors acutely stimulate the synthesis of adrenal catecholamines. In the present study we measured the effect of quinpirole and dopamine on the hydroxylation of tyrosine in the adrenals, using the method of DOPA (3,4-dihydroxyphenylalanine) accumulation following the administration of the inhibitor of aromatic L-amino acid decarboxylase NSD 1015 (3-hydroxybenzylhydrazyne). In view of the large amounts of catecholamines in the adrenal tissue samples, this necessitated a modification of the method for analysing DOPA. Both quinpirole and dopamine significantly enhanced the rate of DOPA accumulation in the adrenals, indicating stimulation of adrenal tyrosine hydroxylase. The effect of dopamine was blocked by domperidone, a dopamine D2 receptor antagonist that penetrates poorly into the central nervous system. Thus the effect of dopamine, which itself penetrates poorly into the central nervous system, was presumably mediated peripherally. Similarly epinine, i.e. the N-methyl derivative of dopamine, appeared to enhance adrenal catecholamine synthesis, as indicated by an elevated adrenal dopamine level. The data support the view that stimulation of peripherally located dopamine D2-like receptors can enhance the rate of adrenal catecholamine synthesis by stimulating the activity of tyrosine hydroxylase.
Kujacic
M
M
Department of Pharmacology, University of Göteborg, Sweden.
Carlsson
A
A
D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003846:Deoxyepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology*; D006834:Hydrazines / Q000008:administration & dosage / Q000494:pharmacology; D006900:Hydroxylation; D007279:Injections, Subcutaneous; D008297:Male; D009206:Myocardium / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002395:Catecholamines; D018491:Dopamine Agonists; D004873:Ergolines; D006834:Hydrazines; D019257:Quinpirole; D014443:Tyrosine; D004294:Domperidone; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase; D003846:Deoxyepinephrine; D004298:Dopamine