Transmitter‐Like Release of Endogenous 3,4‐Dihydroxyphenylalanine from Rat Striatal Slices

Goshima, Yoshio; Kubo, Takao; Misu, Yoshimi

doi:10.1111/j.1471-4159.1988.tb02470.x

Cited by 105 publications

(34 citation statements)

References 21 publications

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“…The release ratios, Spa/Sp1 and S2/S1, were slightly decreased ( Table 2). The impulse-evoked release of DA from rat brain slices obtained in a design similar to that of the present experiments was Cat+-dependent and tetrodotoxin-sensitive (8,14). (-)-Isoproterenol at 10 to 300 nM, a non-selective /3-adrenoceptor agonist, facilitated the evoked release of DA in a concentration-dependent manner (Fig.…”

Section: Resultssupporting

confidence: 72%

“…Through platinum spiral electrodes set up at the two ends of the chamber, electrical field stimulations with alternative pulses (2 Hz, 2 msec, 25 V, 3 min) were performed twice, at 60 (S1) and 90 (S2) min after the start of superfusion, using an electrical stimulator with an isolator (SEN-3201 and SS-102J, Nihon Kohden) (8). Three-min samples were successively collected.…”

Section: Methodsmentioning

confidence: 99%

“…It is generally accepted that the actions of L-DOPA are mediated via its conversion to dopamine (DA) by L-aromatic amino acid decarboxylase (AADC) (2), and this conversion initiates the accumulation of DA in the striata of humans (3) and rats (4), displacement of 3H -DA (5) , and impulse-evoked release of 3H-DA (6) from rat brain slices. On the contrary, we have proposed that L-DOPA is an endogenous neuroactive substance (7)(8)(9)(10)(11). In the course of studies on presynaptic regulatory mechanisms for the release of endogenous catecholamines from rat brain slices (12)(13)(14), we found that endogenous DOPA is released in response to depolarizing stimuli such as bipolar electrical field pulses, high K+ (8) and nicotine (11) from rat striatal slices in a transmitter-like manner.…”

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confidence: 99%

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Nanomolar L-DOPA facilitates release of dopamine via presynaptic .BETA.-adrenoceptors: Comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated C57 black mice, an animal model for parkinson's disease.

Goshima¹,

Misu²,

Arai

et al. 1991

Jpn.J.Pharmacol

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ABSTRACT-Effects of L-DOPA (0.1-10,000 nM) on spontaneous release (Sp), evoked release (S) and tissue content (C) of dopamine (DA) were studied comparatively in superfused striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice to obtain evidence for L-DOPA-induced facilitation of S via presynaptic 8-adrenoceptors. In control slices, isoproterenol-induced concentration-dependent increases in S were propranolol-sensitive. L-DOPA at 0.1-3 nM tended to increase the S of DA with a concomitant tendency of increases in Sp. L-DOPA at 10 -1 X 104 nM concentration-dependently increased Sp. L-DOPA at 1-10 ,u M tended to increase S and 10 ,u M increased C. In slices from MPTP-treated mice, the absolute amounts of Sp, S and C decreased by half compared to those in control slices. L-DOPA at 3 nM facilitated S without increasing Sp. This facilitation was antagonized by propranolol at 3 nM. L-DOPA at 30 nM decreased S from the peak facilitation, which contrasted with no effect in the control slices. However, 10-100 nM L-DOPA increased Sp more markedly than that in the control slices. L-DOPA at 100 nM increased S and C, which contrasted with no effect in the control slices. In conclusion, nanomolar L-DOPA facilitates the S of DA via presynaptic /9-adrenoceptors at concentrations lower than those required to induce conversion to DA even in striatal slices from the MPTP-treated mice model for Parkinson's disease. In model slices, susceptibilities of the Sp, S and C of DA to exogenous L-DOPA could be determined by a balance between degeneration-induced reduction in DOPAdecarboxylase activities and "up-regulation" on the activities of surviving DA neurons.

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Section: Resultssupporting

confidence: 72%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Nanomolar L-DOPA facilitates release of dopamine via presynaptic .BETA.-adrenoceptors: Comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated C57 black mice, an animal model for parkinson's disease.

Goshima¹,

Misu²,

Arai

et al. 1991

Jpn.J.Pharmacol

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“…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)(2)(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).…”

mentioning

confidence: 67%

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

Sato

Okumura

Goshima

et al. 1993

Japanese Journal of Pharmacology

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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...

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“…In con trast to this, we have proposed that DOPA itself is a neu ro-transmitter and/or -modulator in the central nervous system. Depolarizing stimuli released endogenous trans mitter-like DOPA from rat striatal slices (2,3). A trans mitter-like basal DOPA release was seen under physiologi cal conditions in the striata of conscious rats (4).…”

mentioning

confidence: 93%

Dissociation of Cyclic GMP Level from Relaxation of the Distal, but Not the Proximal Colon of Rats

Nakamura

Goshima

Yue

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-The relevance of endogenously released DOPA to the (±)-nicotine-induced increase in loco motor activities was explored in rats. This increase was dose (0.1-1.0 mg/kg, s.c.)-dependent, stereo selective and mecamylamine (1.0 mg/kg, s.c.)-sensitive, but was not antagonized by L-dopa methyl ester (200 pg, i.v.t.), a competitive L-dopa antagonist. Then, by microdialysis, low doses of a-methyl p-tyrosine (a-MPT, i.p.) at 1-10 mg/kg, were tested to find a dose that selectively inhibits the basal DOPA release in the striata: the release was consistently inhibited by 3 mg/kg without any tendency to inhibit the basal dopa mine release. Pretreatment with this dose did inhibit the nicotine-induced increases in locomotor activities. This suggests that endogenously released DOPA is in part relevant to the nicotine-induced behavior in rats.Keywords: DOPA (endogenous neuroactive substance), Nicotine (increase in locomotor activity), a-Methyl p-tyrosine L-3,4-Dihydroxyphenylalanine (L-dopa) is believed to exert its actions via conversion to dopamine (DA) by L aromatic amino acid decarboxylase (AADC) (1). In con trast to this, we have proposed that DOPA itself is a neu ro-transmitter and/or -modulator in the central nervous system. Depolarizing stimuli released endogenous trans mitter-like DOPA from rat striatal slices (2, 3). A trans mitter-like basal DOPA release was seen under physiologi cal conditions in the striata of conscious rats (4). On the other hand, in in vitro rat brain slices (5 7), exogenous nanomolar L-dopa itself stereo selectively facilitated the evoked release of DA and noradrenaline (NA) via pro pranolol-sensitive presynaptic (3-adrenoceptors even un der complete inhibition of AADC. However, this facilita tion was antagonized competitively by L-dopa methyl es ter, whereas it was noncompetitively antagonized by pro pranolol (7). Then, picomolar L-dopa itself stereoselective ly potentiated the isoproterenol-induced facilitation of the NA release (8). This potentiation was selectively an tagonized by L-dopa methyl ester, whereas propranolol an tagonized both the facilitation by isoproterenol alone and its potentiation by L-dopa. Thus, there exists a recogni tion site for DOPA itself, which differs from presynaptic Nicotine releases various neuro-transmitters or -modu lators in the central and peripheral nervous systems. Peripheral application of nicotine increases locomotor ac tivities of rats (10), and this increase seems to be linked to the DA release (11). On the other hand, local perfusion of nicotine into the rat striatum released transmitter-like DOPA via tonically functioning nicotinic acetylcholine receptors (12). Thus, we have attempted to clarify whether i.v.t.-application of L-dopa methyl ester an tagonizes nicotine-induced increases in locomotor activ ities and then whether endogenously released DOPA is relevant to this behavior in rats.Male Sprague-Dawley rats (300-400 g) were given food pellets and water ad libitum and kept on a regular day and night schedule (lights on at 5:00 hr and off a...

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Transmitter‐Like Release of Endogenous 3,4‐Dihydroxyphenylalanine from Rat Striatal Slices

Cited by 105 publications

References 21 publications

Nanomolar L-DOPA facilitates release of dopamine via presynaptic .BETA.-adrenoceptors: Comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated C57 black mice, an animal model for parkinson's disease.

Nanomolar L-DOPA facilitates release of dopamine via presynaptic .BETA.-adrenoceptors: Comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated C57 black mice, an animal model for parkinson's disease.

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

Dissociation of Cyclic GMP Level from Relaxation of the Distal, but Not the Proximal Colon of Rats

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