Tags

Type your tag names separated by a space and hit enter

Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes.
Synapse. 2003 Aug; 49(2):125-33.S

Abstract

Amphetamine has been shown to increase striatal particulate protein kinase C (PKC) activity [Giambalvo (1992b) Neuropharmacology 31:1211-1222]. The present study examined possible mechanisms involved. Specifically, the effects of calcium, endogenous DA, and DA receptors on the amphetamine-induced increase in PKC activity in striatal synaptoneurosomes were examined. Naïve rats and rats pretreated with N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinolone (EEDQ, i.p.), a nonselective irreversible receptor antagonist, or with alpha-methyl-p-tyrosine (AMPT, i.p.), a DA synthesis inhibitor, were sacrificed and striatal synaptoneurosomes were prepared. The tissue was incubated with amphetamine, with and without calcium, and PKC activity was then determined by the endogenous phosphorylation of endogenous substrate proteins, as described previously [Giambalvo (1988a) Biochem Pharmacol 37:4001-4007]. It was found that calcium enhanced the effect of amphetamine on PKC activity, even in rats pretreated with EEDQ. Intracellular calcium was required since pretreatment with 1,2-bis (2-aminophenoxy) ethane-N, N, N, N-tetracetic acid acetoxymethyl ester (BAPTA-AM) in vitro attenuated the amphetamine-induced increase in PKC activity, resulting in an inhibition of PKC activity instead. Likewise, endogenous DA was essential since pretreatment with AMPT resulted in a similar amphetamine-induced inhibition of PKC activity. Pretreatment with AMPT did not alter the inhibitory effect of the D2 DA agonist, LY 171555, on PKC activity. It did, however, abolish the calcium-dependent stimulatory effect of the D1 agonist SKF 38393 on PKC activity, rendering it inhibitory regardless of calcium. Considering that both BAPTA-AM and AMPT pretreatments, which diminished DA release without affecting uptake via different mechanisms, produced similar inhibitory effects on PKC activity by amphetamine, these results suggest that the inward transport of amphetamine had an inhibitory effect on PKC activity. In contrast, the outward transport of DA seemed to have a stimulatory effect on PKC activity since incubation with low sodium or with ouabain, conditions that promote DA reverse-transport, increased PKC activity. These results showed that PKC activity was altered differently during inward vs. outward transport. The amphetamine-induced increase in PKC activity was attenuated by pretreatment with DA uptake blockers (nomifensine, GBR 12935, and bupropion), even though these drugs by themselves also increased PKC activity. This effect was diminished by calcium and persisted in rats pretreated with EEDQ. Thus, calcium had a differential effect on the PKC activity induced by a transported substrate (amphetamine) vs. nontransported inhibitors (DA uptake blockers).

Authors+Show Affiliations

Rhode Island Psychiatric Research Center, Eleanor Slater Hospital, Cranston, Rhode Island 02920, USA.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12740868

Citation

Giambalvo, Cecilia T.. "Differential Effects of Amphetamine Transport Vs. Dopamine Reverse Transport On Particulate PKC Activity in Striatal Synaptoneurosomes." Synapse (New York, N.Y.), vol. 49, no. 2, 2003, pp. 125-33.
Giambalvo CT. Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes. Synapse. 2003;49(2):125-33.
Giambalvo, C. T. (2003). Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes. Synapse (New York, N.Y.), 49(2), 125-33.
Giambalvo CT. Differential Effects of Amphetamine Transport Vs. Dopamine Reverse Transport On Particulate PKC Activity in Striatal Synaptoneurosomes. Synapse. 2003;49(2):125-33. PubMed PMID: 12740868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes. A1 - Giambalvo,Cecilia T, PY - 2003/5/13/pubmed PY - 2003/8/9/medline PY - 2003/5/13/entrez SP - 125 EP - 33 JF - Synapse (New York, N.Y.) JO - Synapse VL - 49 IS - 2 N2 - Amphetamine has been shown to increase striatal particulate protein kinase C (PKC) activity [Giambalvo (1992b) Neuropharmacology 31:1211-1222]. The present study examined possible mechanisms involved. Specifically, the effects of calcium, endogenous DA, and DA receptors on the amphetamine-induced increase in PKC activity in striatal synaptoneurosomes were examined. Naïve rats and rats pretreated with N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinolone (EEDQ, i.p.), a nonselective irreversible receptor antagonist, or with alpha-methyl-p-tyrosine (AMPT, i.p.), a DA synthesis inhibitor, were sacrificed and striatal synaptoneurosomes were prepared. The tissue was incubated with amphetamine, with and without calcium, and PKC activity was then determined by the endogenous phosphorylation of endogenous substrate proteins, as described previously [Giambalvo (1988a) Biochem Pharmacol 37:4001-4007]. It was found that calcium enhanced the effect of amphetamine on PKC activity, even in rats pretreated with EEDQ. Intracellular calcium was required since pretreatment with 1,2-bis (2-aminophenoxy) ethane-N, N, N, N-tetracetic acid acetoxymethyl ester (BAPTA-AM) in vitro attenuated the amphetamine-induced increase in PKC activity, resulting in an inhibition of PKC activity instead. Likewise, endogenous DA was essential since pretreatment with AMPT resulted in a similar amphetamine-induced inhibition of PKC activity. Pretreatment with AMPT did not alter the inhibitory effect of the D2 DA agonist, LY 171555, on PKC activity. It did, however, abolish the calcium-dependent stimulatory effect of the D1 agonist SKF 38393 on PKC activity, rendering it inhibitory regardless of calcium. Considering that both BAPTA-AM and AMPT pretreatments, which diminished DA release without affecting uptake via different mechanisms, produced similar inhibitory effects on PKC activity by amphetamine, these results suggest that the inward transport of amphetamine had an inhibitory effect on PKC activity. In contrast, the outward transport of DA seemed to have a stimulatory effect on PKC activity since incubation with low sodium or with ouabain, conditions that promote DA reverse-transport, increased PKC activity. These results showed that PKC activity was altered differently during inward vs. outward transport. The amphetamine-induced increase in PKC activity was attenuated by pretreatment with DA uptake blockers (nomifensine, GBR 12935, and bupropion), even though these drugs by themselves also increased PKC activity. This effect was diminished by calcium and persisted in rats pretreated with EEDQ. Thus, calcium had a differential effect on the PKC activity induced by a transported substrate (amphetamine) vs. nontransported inhibitors (DA uptake blockers). SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/12740868/Differential_effects_of_amphetamine_transport_vs__dopamine_reverse_transport_on_particulate_PKC_activity_in_striatal_synaptoneurosomes_ L2 - https://doi.org/10.1002/syn.10223 DB - PRIME DP - Unbound Medicine ER -