title: Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue.
abstract: The present study examined the effect of a selective delta-opioid receptor agonist [D-Ala2-D-Leu5] enkephalin (DADL) on the spontaneous and the L-glutamic acid (L-Glu)-evoked release of endogenous dopamine from superfused slices of rat caudate-putamen. The amount of dopamine in slice superfusates was measured by a sensitive method employing high-performance liquid chromatography with electrochemical detection (h.p.l.c.-e.d.) after a two-step separation procedure. The spontaneous release of endogenous dopamine was partially dependent on Ca2+, enhanced in Mg2+-free superfusion medium, partially reduced by tetrodotoxin (TTX, 0.3 microM), partially reduced by the putative excitatory amino acid receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (DL-APH, 1 mM), and increased 10 fold by the dopamine uptake blocker, nomifensine (10 microM). DADL (5 and 50 nM) did not significantly affect spontaneous dopamine release. L-Glu (0.1-10 mM) produced a concentration-dependent release of endogenous dopamine from slices of caudate-putamen. This effect was Ca2+-dependent, strongly inhibited by 1.2 mM Mg2+, attenuated by DL-APH (1 mM), attenuated by TTX (0.3 microM), and enhanced by nomifensine (10 microM). In the presence of nomifensine DADL (50 nM) reduced significantly the L-Glu-evoked release of endogenous dopamine by 20%. The inhibitory effect of DADL was blocked by 10 microM naloxone. These results indicate that L-Glu stimulates the Ca2+-dependent release of endogenous dopamine in the caudate-putamen by activation of N-methy-D-aspartate-type of excitatory amino acid receptors. This release can be selectively modified by the delta-opioid agonist DADL in a naloxone-sensitive manner.
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D009627:Nomifensine; D018698:Glutamic Acid; D013779:Tetrodotoxin; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D015763:2-Amino-5-phosphonovalerate; D008274:Magnesium; C031231:2-amino-7-phosphonoheptanoic acid; D004298:Dopamine