Relationship between tyrosine hydroxylase content and noradrenergic cell reactivity to piperoxane: an in vivo voltammetric approach in the rat locus coeruleus.
A previous electrochemical study showed that the increase in the tyrosine hydroxylase (TH) content of the locus coeruleus (LC) produced by RU24722 administration was associated with a relative decrease in the catecholaminergic metabolic reactivity of this nucleus to a hypotensive stimulus. Since alpha 2 receptors participate in the regulation of the activity of both LC neurons and TH, the aim of the present work was to evaluate the possible involvement of the autoinhibition mediated by alpha 2 autoreceptors in the inverse relationship between the reactivity of the LC and its TH content. Our study was divided into two successive steps: (i) the electrochemical measurement of the in vivo metabolic activation of LC cells in response to alpha 2-adrenergic receptor blockade, and (ii) the evaluation of the quantity of TH every 100 microns along the caudorostral axis in each recorded LC. The capacity of TH protein to be activated was evaluated by the measurement, using differential normal pulse voltammetry, of the in vivo variations of the extracellular 3,4-dihydroxyphenylacetic acid concentrations in response to six cumulated doses of the alpha 2-antagonist piperoxane. The corresponding dose-response curves, determined in control- and RU24722-treated rats, were expressed as a function of the quantity of TH contained either in the whole recorded LC or in the 100 microns-wide coronal interval surrounding the recording site. It was established that the slopes of the dose-response curves were significantly (P < 0.01) and inversely related to the quantity of TH at the level of the recording site. This result suggests that the negative control of the catecholaminergic metabolic reactivity in a restricted area of the LC could be directly or indirectly dependent on the level of expression of TH protein in this particular area.
Vachette
C
C
Universitè Claude Bernard, Laboratoire de Neuropharmacologie, Faculté de Pharmacie, Lyon, France.
Debure
L
L
Rousset
C
C
Pujol
J F
JF
Renaud
B
B
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002396:Catechols / Q000493:pharmacokinetics; D004563:Electrochemistry; D006207:Half-Life; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D010084:Oxidation-Reduction; D010883:Piperoxan / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis*
D002396:Catechols; D015102:3,4-Dihydroxyphenylacetic Acid; D010883:Piperoxan; D014446:Tyrosine 3-Monooxygenase; C034221:catechol; D009638:Norepinephrine