Effect of Systemic Anaphylaxis on the Hepatic Drug-Metabolizing System in Rats

Abstract

ABSTRACT-L-Dopa is a potentiator for presynaptic ~-adrenoceptors. We studied whether L-dopa poten tiates the activities of other presynaptic receptors to modulate the evoked noradrenaline (NA) release in rat hypothalamic slices. UK14304 (0.1-1 riM), a selective a2-agonist, concentration-dependently inhibited NA release. Noneffective 10 PM L-dopa potentiated the UK14304-induced inhibition. This potentiation was selectively antagonized by 1 nM L-dopa methyl ester, a competitive L-dopa antagonist, while yohimbine an tagonized both the inhibition by UK14304 alone and its potentiation by L-dopa. However, 10 PM L-dopa produced no effect on angiotensin II (0.1-1 nM)-induced facilitation. L-Dopa potentiates activities of presynaptic ~ and a2-adrenoceptors but not those of angiotensin II receptors on rat hypothalamic NA neurons.Keywords: DOPA (endogenous neuroactive substance), Presynaptic a2-adrenoceptor, Noradrenaline release (rat hypothalamic slices) L-Dopa is believed to be an inert amino acid that exerts its actions through its conversion to dopamine (DA) by aromatic L-amino acid decarboxylase (AADC). Contrary to this generally accepted idea, we found that endogenous L-dopa is released in a transmitter-like manner from in vitro and in vivo rat striata (1-3). On the other hand, even under essentially complete inhibition of AADC, nanomolar concentrations of L-dopa stereo selectively facilitate via presynaptic (3-adrenoceptors the impulse evoked release of noradrenaline (NA) and DA from rat brain slices (4 7). The important finding is that this facili tation of the NA release is antagonized competitively by L-dopa methyl ester, while it is antagonized noncompeti tively by propranolol in rat hypothalamic slices (7). Fur thermore, picomolar concentrations of L-dopa, which alone produce no effect, stereoselectively potentiate the isoproterenol-induced facilitation of the NA release (8). This potentiation was selectively antagonized by L-dopa methyl ester, whereas propranolol antagonized both the facilitation by isoproterenol alone and its potentiation by L-dopa. Thus, there exists a recognition site for L-dopa it self, which differs from presynaptic (3-adrenoceptors. In addition to the presynaptic actions, we recently found that L-dopa but not DA microinjected into in vivo rat nucleus tractus solitarii produced L-dopa methyl ester-sen sitive depressor and bradycardic responses (9). These responses are not modified by pretreatment with an AADC inhibitor and with intraventricular 6-hydroxydo pamine, thereby indicating that the actions of L-dopa it self are postsynaptic in nature. All of these findings sup port the hypothesis that L-dopa is a neurotransmitter or modulator in the rat central nervous system. L-Dopa is a potentiator for presynaptic facilitatory ~3 adrenoceptors (8). It is an important subject to study whether or not this event is universally valid for the other types of receptors. Here, we studied whether or not L dopa potentiates functions of presynaptic inhibitory a2 adrenoceptors (10) and facilitatory angiot...

Endogenously released DOPA is a causal factor for glutamate release and resultant delayed neuronal cell death by transient ischemia in rat striata

“…1991b). Ten picomolar DOPA potentiates inhibition of norepinephrine release by 0.1–1 µ m 5‐bromo‐6‐(2‐imidazolin‐2‐ylamino)‐quinoxaline , an α 2 ‐agonist, via presynaptic α 2 ‐adrenoceptors (Sato et al . 1993).…”

Prejunctional angiotensin receptors involved in the facilitation of noradrenaline release in mouse tissues

“…In agreement with the present study, angiotensin II failed to alter the depolarization‐evoked release of noradrenaline in rat occipital cortex ( Taube et al ., 1977 ), hypothalamus ( Taube et al ., 1977 ; Meldrum et al ., 1984 ; Meldrum & Westfall, 1986 ) and locus coeruleus ( Huang et al ., 1987 ). Other authors have reported that angiotensin enhances depolarization‐evoked noradrenaline release in rabbit ( Garcia‐Sevilla et al ., 1979 ) and rat hypothalamus ( Sato et al ., 1993 ) and rat parietal cortex ( Huang et al ., 1987 ). The present negative findings with angiotensin contrast with the expected release‐enhancing effect of phentolamine in the hypothalamus.…”