|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1989 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine synthesis, and it converts tyrosine to L-DOPA. In recent years, several groups of investigators have reported that TH-immunoreactivity is detleted not only in well-known catecholaminergic neurons but also in noncatecholaminergic neurons. In the present study, we investigated these ectopic TH neurons by asensitive immunocytochemical method, and presented the possibility that some of these neurons produce L-DOPA as an endproduct.
(1) The immunocytochemical distribution of L-DOPA immunoreactive neurons and their ability to uptake L-DOPA were investigated in the rat hypothalamus. Weakly L-DOPA-immunoreactive (IR) neurons were detected in the classical dopaminergic cell groups (A11, A12, A13, and A14). Strongly L-DOPA-IR neurons were found in the ventrolateral part of the arcuate nucleus, periarcuate region just dorsal to the ventral surface of the brain (VLAR/PA), periventricular area of the anterior hypothalamus, and caudal part of the arcuate nucleus. Intraperitoneal treatment with reserpine (10 mg/kg), peripheric amino acid decarboxylase (AADC) inhibitor (Ro4-4602), and L-DOPA (50 mg/kg) induced dopamine immunoreactivity in neurons, which distribution was coincident with that of AADC-containing neurons. However, these treatments could not induce dopamine-IR neurons in VLAR/PA. The present finding suggests that the decarboxylating activity in strongly stained L-DOPA neurons is zero or very low, and further supports the hypothesis that these neurons produce L-DOPA as an end product.
(2) In the hypothalamus of Japanese monkey (macaca fuscata), non-catecholaminergic TH-IR neurons were detected in the caudal part of the paraventricular nucleus and the ventrolateral part of the infundibular nucleus.
(3) In in situ hybridization study using cDNA probes of rat TH, TH mRNA positive cells showed the similar distribution pattern of TH-IR neurons.