Evidence for protein kinase-C mediation of the neurotensin-induced activation of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons.
The purpose of the present study was to determine whether neurotensin acts within the arcuate nucleus/median eminence to activate tyrosine hydroxylase (TH) within tuberoinfundibular dopamine neurons. The role of Ca2+/phospholipid-dependent protein kinase (protein kinase-C) in the regulation of TH and its involvement in the neurotensin-induced activation of TH within tuberoinfundibular dopamine (TIDA) neurons also was investigated. The activity of TH within TIDA neurons was assessed by quantification of the formation of 3,4-dihydroxyphenylalanine in the arcuate nucleus/median eminence after inhibition of 3,4-dihydroxyphenylalanine decarboxylase. Neurotensin (0.1-10 nM) increased the activity of TH within the arcuate nucleus/median eminence under in vitro conditions by approximately 80%. The activity of TH in the arcuate nucleus/median eminence also was increased approximately 55% by the phorbol ester 12-O-tetradecanoyl(phorbol-13-acetate) (1-100 nM), which activates protein kinase-C. Sphingosine (10 microM), an inhibitor of protein kinase-C, attenuated the activation of TH within TIDA neurons that was induced by both 12-O-tetradecanoyl(phorbol-13-acetate) and neurotensin. Sphingosine alone did not alter the activity of TH, nor did it alter the (Bu)2cAMP-induced activation of TH in the arcuate nucleus/median eminence. It is concluded that neurotensin acts directly within the arcuate nucleus/median eminence to activate TIDA neurons. Furthermore, it is suggested that the activity of TH within these neurons is enhanced after the activation of protein kinase-C and that protein kinase-C may mediate the neurotensin-induced activation of TH within these hypothalamic dopamine neurons.
Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106.
S A
SA
Berry
G A
GA
Gudelsky
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D004789:Enzyme Activation; D006834:Hydrazines / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D006834:Hydrazines; D009496:Neurotensin; D004295:Dihydroxyphenylalanine; D003994:Bucladesine; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine