• Toxicological Research
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• v.6 no.1
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• pp.75-88
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• 1990

The characteristics of dopamine uptake, D-1 and D-2 receptors after acute and subacute cocaine administration were determind in striatum from WKY and SHR. Cocaine was administered either acutely (40 mg/kg, s.c.) or twice daily (20 mg/kg, s.c.) for 3 and 7 days in 9-wk old WKY and SHR. Rats were sacrificed 30 min, 2 or 24 h after the single injection and 18 h after the last administration to the subacutely treated group. The changes in dopamine uptake, dopamine uptake sites, D-1 and D-2 receptors were determined using $(^3H)$dopamine, $(^3H)$-GBR-12935, $(^3H)$SCH-23390 and $(^3H)$sulpiride, respectively. In acutely treated rats, significant increases in $V_{max}$of dopamine uptake were observed 30 min after the cocanine injection in both strains without changes in $K_m$ values. The in vitro $IC_{50}$for cocaine was significantly decreased 30 min in WKY and 2 h in SHR. However, that for in vitro GBR-12909 was significantly increased 30 min and 2 h in both strains. Also densities of $(^3H)$-GBR-12935 binding sites were significantly increased 30 min and 2 h without changes in their $K_d$. Significant increases in D-2 receptor density were observed 30 min, 2 or 24 h after acute injection in both strains without changes in their affinities. The density of D-1 receptor was significantly decreased 30 min after the injection in WKY, but not in SHR. In subacutely treated rats, a significant increase in $K_m$ of dopamine uptake was observed in 7-day treated SHR. The in vitro $IC_{50}$fot GBR-12909 was significantly increased in 3-day treated WKY. The density of D-1 receptors was significantly increased in 3- and 7-day treated WKY, but not in SHR. The affinity of both binding sites remained unchanged. The results suggest that cocanine administration alters dopamine uptake, characteristics of dopamine uptake sites and dopamine receptor binding characteristics in rat brain. Furthermore, D-1 and D-2 dopamine receptors appear to be differently regulated.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.475-481
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• 2016

PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine $D_3$ receptors ($D_3R$), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine $D_2$ receptor ($D_2R$) and $D_3R$ in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of $D_2R$ were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of $D_3R$ were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on $D_3R$ functions.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.49-61
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• 1985

In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.