Neuropeptide Y induced modulation of dopamine synthesis in the striatum.
The purpose of the present study was to determine whether the activation of NPY receptors alters catecholamines (CA) synthesis in the central nervous system and, if so, to identify the NPY receptor subtype(s) mediating this effect. Tyrosine hydroxylation, the rate-limiting step in CA synthesis, was assessed by measuring the accumulation of 3,4-dihydroxyphenyalanine (DOPA) by high pressure liquid chromatography coupled to electrochemical detection (HPLC-EC) in rat striatal dices following incubation of the tissue with the aromatic L-amino acid decarboxylase inhibitor m-hydroxybenzyl hydrazine (NSD 1015). Treatment with NSD 1015 resulted in an increase in DOPA accumulation that was increased even further following depolarization with a high potassium (KCl) buffer. PYY13-36 and NPY13-36 both produced a significant enhancement of the KCl-induced increase in DOPA accumulation. The effect of PYY13-36 was completely attenuated by the selective Y2 antagonist BIIE0246 suggesting that activation of Y2 receptors enhanced the synthesis of dopamine. In contrast to the effects of NPY13-36 and PYY13-36; NPY, PYY and PYY3-36 all produced a significant attenuation of the KCl-induced increase in DOPA accumulation. The Y1 antagonist BIBO3304 and the Y5-antagonist CGP71683A, both prevented the inhibitory effect of NPY converting it to a stimulatory effect. The enhancement of the NPY induced increase in DOPA accumulation observed by BIBO3304 was attenuated when examined in the presence of the Y2 antagonist BIIE0246. These results suggest that activation of NPY receptors can modulate the synthesis of CA in the rat striatum. The Y1 and Y5 receptor appear to be involved in attenuation, while Y2 receptors are involved in the stimulation of synthesis.
Adewale
Adepero Shola
AS
Saint Louis University School of Medicine, Department of Pharmacological and Physiological Science, 1402 South Grand Blvd, Saint Louis, MO 63104, USA.
Macarthur
Heather
H
Westfall
Thomas C
TC
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000032:analysis / Q000096:biosynthesis; D004298:Dopamine / Q000096:biosynthesis*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D019894:Peptide YY / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C078948:peptide YY (13-36); D019894:Peptide YY; C061785:peptide YY (3-36); D004295:Dihydroxyphenylalanine; D004298:Dopamine