Dopamine and L-dopa: inhibition of thyrotropin-stimulated thyroidal thyroxine release.
Previous studies had suggested that norepinephrine (NE) and its precursors dopamine (DA) and L-DOPA acted similarly on iodine metabolism of isolated thyroid cells. Present studies indicate that this similarity extends to the inhibition by catecholamines of TSH-stimulated T4 release by mouse thyroids incubated in vitro. DA (5 X 10(-4) M), like NE, shown previously, inhibits TSH-stimulated T4 release. This inhibition was reversed by the alpha-blockers phentolamine, prazosin, and yohimbine, but not by the beta-blocker L-propranolol. DU-18288 and diethyldithiocarbamate, inhibitors of DA beta-hydroxylase, did not reduce DA inhibition, suggesting that prior conversion to NE was not a condition for DA activity. Apomorphine, a dopaminergic agonist but not a NE precursor, acted like DA, and its inhibition was also reversed by alpha-blockers. Furthermore, sulpiride, a dopaminergic blocker, reversed DA and apomorphine inhibition of TSH stimulation. These results suggest that DA inhibits TSH-stimulated T4 release through both adrenergic and dopaminergic receptors. On the other hand, L-DOPA, exerting an inhibition like that of DA, was also reversed by alpha-blockers, but its activity was greatly diminished by carbidopa, an inhibitor of aromatic L-amino acid decarboxylase, the enzyme converting L-DOPA to DA. This indicated that L-DOPA had to be converted to DA for activity. Both DA and L-DOPA inhibited stimulation of T4 release induced by (Bu)2cAMP, suggesting that their effect was exerted at a locus distal to cAMP generation. Indirect confirmation of a cAMP-independent pathway was obtained when DA inhibited TSH-stimulated cAMP formation, but, contrary to T4 release, this inhibition was not reversed by dopaminergic or adrenergic blockers. Presumably, therefore, DA inhibition of TSH-stimulated cAMP production was not related to T4 release. We conclude that 1) DA inhibits TSH-stimulated T4 release in mouse thyroids via alpha-adrenergic and dopaminergic receptors; 2) L-DOPA has to be converted to DA to produce inhibition; and 3) cAMP is unlikely to be an intermediary in DA inhibition.
Maayan
M L
ML
Sellitto
R V
RV
Volpert
E M
EM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001285:Atropine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D005260:Female; D007980:Levodopa / Q000494:pharmacology*; D051379:Mice; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D013974:Thyroxine / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D007980:Levodopa; D003994:Bucladesine; D001285:Atropine; D013469:Sulpiride; D013972:Thyrotropin; D000242:Cyclic AMP; D004299:Dopamine beta-Hydroxylase; D002230:Carbidopa; D001058:Apomorphine; D013974:Thyroxine; D004298:Dopamine