caa a22 4500 469079088 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF00164579 doi (NATIONALLICENCE)springer-10.1007/BF00164579 α2 Autoreceptor-mediated modulation of tyrosine hydroxylase activity in noradrenergic regions of the rat brain in vivo [Elektronische Daten] [Francisca Pi, Jesús García-Sevilla] 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. Springer-Verlag, 1992 Brain α2-autoreceptors nationallicence DOPA/noradrenaline synthesis nationallicence Clonidine nationallicence Idazoxan nationallicence Adrenergic drugs nationallicence Pi Francisca Sección de Farmacología, Departamento de Neurociencias, Universidad del País Vasco, Leioa, Bizkaia, Spain aut García-Sevilla Jesús Sección de Farmacología, Departamento de Neurociencias, Universidad del País Vasco, Leioa, Bizkaia, Spain aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 653-660 0028-1298 345:6<653 1992 345 210 https://doi.org/10.1007/BF00164579 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00164579 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pi Francisca Sección de Farmacología, Departamento de Neurociencias, Universidad del País Vasco, Leioa, Bizkaia, Spain aut NATIONALLICENCE 700 1- García-Sevilla Jesús Sección de Farmacología, Departamento de Neurociencias, Universidad del País Vasco, Leioa, Bizkaia, Spain aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 653-660 0028-1298 345:6<653 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer