부산대학교 도서관

Summary:The physiological importance of brain α2-adrenoceptors in controlling the activity of tyrosine hydroxylase in noradrenergic regions was investigated using the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition as a measure of the rate of tyrosine hydroxylation (and synthesis of noradrenaline) in vivo. In the hypothalamus and cerebral cortex, clonidine (0.025–1 mg/kg, i.p.) decreased (18%–43%) and idazoxan (0.1–80 mg/kg, i.p.) increased (20%–73%) the synthesis of DOPA in a dose-dependent manner. Moreover, pretreatment with idazoxan (0.1 mg/kg) antagonized the effect of clonidine (0.1 mg/kg) in the hypothalamus. After treatment with reserpine (5 mg/kg, s.c., 18 h before decapitation) and depletion of noradrenaline, clonidine (0.5 mg/kg) continued to decrease (50%–55%) but idazoxan (20 mg/kg) failed to increase the synthesis of DOPA, which suggested the involvement of an α-autoreceptor mechanism. Acute treatments of rats (not exposed to reserpine) with a wide variety of adrenoceptor agonists such as guanfacine 6, B-HT 920, xylazine, bromoxidine (1 mg/kg) and antagonists such as yohimbine, phentolamine, prazosin (10 or 20 mg/kg) resulted in significant decreases (15%–55%) or increases (21%–99%) in the synthesis of DOPA in both brain regions. However, other agonists (oxymetazoline, azepexole, tramazoline, methoxamine) and antagonists (tolazoline, dihydroergotamine, phenoxybenzamine, propranolol) did not modify the synthesis of DOPA. In the hypothalamus and cerebral cortex the effects of the drugs were consistent with the selectivity of α-adrenoceptor agonists and antagonists (except prazosin) for an α2-adrenoceptor. The results also suggest that the α2-autoreceptor that modulates the synthesis of noradrenaline in the rat brain appears to belong to the prazosin-sensitive α2B-subtype.