In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 44, No. 12 ( 2011-04-12), p. 990-995
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2042-7158
,
0022-3573
DOI:
10.1111/j.2042-7158.1992.tb07080.x
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2011
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
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