L-Dopa-like Regulatory Actions of l-threo-3,4-Dihydroxyphenylserine on the Release of Endogenous Noradrenaline Via Presynaptic Receptors in Rat Hypothalamic Slices

Autor: Jin-Liang Yue, Yoshio Goshima, Yoshimi Misu, Shinichi Nakamura
Rok vydání: 1992
Předmět:
Zdroj: Journal of Pharmacy and Pharmacology. 44:990-995
ISSN: 2042-7158
0022-3573
DOI: 10.1111/j.2042-7158.1992.tb07080.x
Popis: Effects of l-threo-3,4-dihydroxyphenylserine (l-threo-DOPS) on the spontaneous release and the stimulus(2 Hz)-evoked release of endogenous noradrenaline were studied in rat hypothalamic slices with functioning l-aromatic amino acid decarboxylase (AADC) and with AADC inhibition. In non-inhibited slices, spontaneous release was not modified by l-threo-DOPS at 1 Pm-100Nm, tended to increase at 1–10 μm and increased at 100 μm. Noradrenaline tissue content slightly increased at 100 μm. Stimulated release was concentration-dependently facilitated at 1–1000 Pm and tended to decrease gradually from a maximum at 10 Nm-10 μm. Under AADC inhibition, spontaneous release concentration-dependently increased at 10–100 μm by 60% of the increase seen in slices without AADC inhibition. Increase in noradrenaline tissue content was abolished. l-threo-DOPS produced a triphasic pattern on stimulated release; concentration-dependent facilitation at 1–1000 Pm similar to that seen in slices with functional AADC, no facilitation at 10–1000 Nm, and a concentration-dependent increment at 10–100 μm. The facilitation at 1 Nm was stereoselective and was antagonized by (–)-propranolol 10 Nm, and no facilitation at 100 Nm was restored to the maximum by yohimbine 10 Nm, DG-5128 10 Nm or S-sulpiride 1 Nm. Furthermore, l-threo-DOPS (1–1000 Pm)-induced facilitation was competitively antagonized by l-dopa methyl ester, a competitive antagonist for l-dopa, with a pA2 value of 13·6, whereas it was noncompetitively antagonized by (–)-propranolol.
Databáze: OpenAIRE
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