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$122 DOPAMINE RELEASE AND METABOLISM IN DAergic CELL-GRAFTED CAUDATE NUCLEUS IN THE RAT. TAKESHI HASHITANI t MICHIKO KUMAZAKIt TERUMI SAKURAI t ISOBE YOSIAKIt FUJIYA FURUYAMA t HARUHIKO SATO AND HITO0 NISHINO. Department of Physiology, Nagoya City University Medical School r Mizuho-ku t Nagoya 467t Japan. A suspension of fetal nigral DAergic cells was grafted to the caudate nucleus of rats with unilateral lesions in the nigrostriatal DA pathway. To investigate the function of grafted cells, we measured the concentration of DA and its metabolites using in vivo microdialysis in freely moving rats. I) Concentration of DA in the dialysate of grafted rats was almost at the same level as that of controls, and those of DOPAC and HVA were 30-50 % of controls. 2) In control rats DA increased to 4 times, and DOPAC and HVA decreased to about 30-40 % of the baseline after methamphetamine (3 mg/kg i.p.) injection. Consequently, the DOPAC/DA or HVA/DA ratio decreased. In grafted rats DA increased to nearly 2 times, but DOPAC and HVA did not decrease significantly. 3) In control rats L- dopa loading increased DA, DOPAC, and HVA to 10, 20, and 20 times baseline (peak, 60, 100, and 160 min after loading, respectively) and decreased thereafter. DA increased again when DOPAC and HVA decreased. In grafted rats DA, DOPAC, and HVA increased with similar time courses of controls, though the responses were small. Data suggest that grafted DAergic cells synthesize and release DA in a similar fashion as those in intact rats. This might be the basis for motor recovery. ACTIONS OF ADENOSINE ON SPONTANEOUS OR EVOKED TRAMSMITTER RELEASE AT THE FROG NEUROMUSCULAR JUNCTION. YORIKO TAKIKAWA, AND NORIKO TAKEUCHI. Department of Physiology, Juntendo University School of Medicin, 2-I-I Hongo, Bunkyou-ku, Tokyo 113 t Japan. The inhibitory effects of adenosine on spontaneous and evoked transmitter release were investigated at the frog neuromuscular junction. Applied adenosine reduced both spontaneous (MEPP) and evoked (EPP) quantal release dose- dependently. In normal and high (12mM) K÷solutions, the degree of inhibition on MEPP frequency produced by adenosine was not markedly changed in a wide range of external Ca~concentrations (0.I-7.2mM), even in solution containing no added Ca and ImM-EGTA. When the spontaneous release included sub-MEPP or giant MEPP, addition of ademosine did not alter the sub-MEPP and giant MEPP frequencies but selectively decreased the normal mode MEPP frequency. Application of adenosine deaminase slightly increased both spontaneous and evoked transmitter release, while the enzyme application appeared to have no apparent effect in some cases of high K+solution. These results suggest the possibilities that I) the depressant effects of adenosine are not mainly caused by reducing Ca~influx into the nerve terminals, 2) there is a release site that is unaffected by adenosine, 3) endogenous adenosine concentration and adenosine deaminase activity might vary from preparation to preparation. ++ Ca -INDEPENDENT REGULATION OF TRANSMITTER RELEASE AT THE FROG NEUROMUSCULAR JUNCTION: 2ND REPORT. NORIKO TANAB._EE *z, AND H1ROMASA KIJIM/_k_ 2, 1Department of Biology, Daiichi College 9._[ Pharmaceutical Sciences, Fukuoka 815, and 2Department. of Biology, Faculty of Science, Kyushu University, Fukuoka 812, Japan. Four processes of stimulation-induced increase in transmitter release have been known at the frog neuromuscular junction (NMJ). We reported last year that two slower processes, augmentation and po- ++ ++ tentiation, occur independently of internal Ca , by making use of the NMJ loaded with a Ca -chelator BAPTA (Tanabe and Kijima, Neurosci. Lett. 99, 147, 19891. Among two other faster processes, the fast facilitation was completely lost at the BAPTA-loaded NMJ, while magnitude of the slow facilitation was unchanged and its decaying time constant was a little increased, compared with the normal NMJ. The ++ augmentation and potentiation of MEPP frequency observed under external Ca -free conditions (+EGTA 1 raM) were also little changed at the BAPTA-loaded NMJ. Three slower stimulation-induced increases of transmitter release were strongly suggested to be caused independently of the internal Ca ++ at the releasing site. Dual release-regulating systems may exist at the NMJ, as well as in the mast cell.

Dopamine release and metabolism in DAergic cell-grafted caudate nucleus in the rat

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$122

DOPAMINE RELEASE AND METABOLISM IN DAergic CELL-GRAFTED CAUDATE NUCLEUS IN THE RAT. TAKESHI HASHITANI t MICHIKO KUMAZAKIt TERUMI SAKURAI t ISOBE YOSIAKIt FUJIYA FURUYAMA t HARUHIKO SATO AND HITO0 NISHINO. Department of Physiology, Nagoya City University Medical School r Mizuho-ku t Nagoya 467t Japan.

A suspension of fetal nigral DAergic cells was grafted to the caudate nucleus of rats with unilateral lesions in the nigrostriatal DA pathway. To investigate the function of grafted cells, we measured the concentration of DA and its metabolites using in vivo microdialysis in freely moving rats. I) Concentration of DA in the dialysate of grafted rats was almost at the same level as that of controls, and those of DOPAC and HVA were 30-50 % of controls. 2) In control rats DA increased to 4 times, and DOPAC and HVA decreased to about 30-40 % of the baseline after methamphetamine (3 mg/kg i.p.) injection. Consequently, the DOPAC/DA or HVA/DA ratio decreased. In grafted rats DA increased to nearly 2 times, but DOPAC and HVA did not decrease significantly. 3) In control rats L- dopa loading increased DA, DOPAC, and HVA to 10, 20, and 20 times baseline (peak, 60, 100, and 160 min after loading, respectively) and decreased thereafter. DA increased again when DOPAC and HVA decreased. In grafted rats DA, DOPAC, and HVA increased with similar time courses of controls, though the responses were small. Data suggest that grafted DAergic cells synthesize and release DA in a similar fashion as those in intact rats. This might be the basis for motor recovery.

ACTIONS OF ADENOSINE ON SPONTANEOUS OR EVOKED TRAMSMITTER RELEASE AT THE FROG NEUROMUSCULAR JUNCTION. YORIKO TAKIKAWA, AND NORIKO TAKEUCHI. Department of Physiology, Juntendo University School of Medicin, 2-I-I Hongo, Bunkyou-ku, Tokyo 113 t Japan.

The inhibitory effects of adenosine on spontaneous and evoked transmitter release were investigated at the frog neuromuscular junction. Applied adenosine reduced both spontaneous (MEPP) and evoked (EPP) quantal release dose- dependently. In normal and high (12mM) K÷solutions, the degree of inhibition on MEPP frequency produced by adenosine was not markedly changed in a wide range of external Ca~concentrations (0.I-7.2mM), even in solution containing no added Ca and ImM-EGTA. When the spontaneous release included sub-MEPP or giant MEPP, addition of ademosine did not alter the sub-MEPP and giant MEPP frequencies but selectively decreased the normal mode MEPP frequency. Application of adenosine deaminase slightly increased both spontaneous and evoked transmitter release, while the enzyme application appeared to have no apparent effect in some cases of high K+solution. These results suggest the possibilities that I) the depressant effects of adenosine are not mainly caused by reducing Ca~influx into the nerve terminals, 2) there is a release site that is unaffected by adenosine, 3) endogenous adenosine concentration and adenosine deaminase activity might vary from preparation to preparation.

++

Ca -INDEPENDENT REGULATION OF TRANSMITTER RELEASE AT THE FROG NEUROMUSCULAR

JUNCTION: 2ND REPORT. NORIKO TANAB._EE *z, AND H1ROMASA KIJIM/_k_ 2, 1Depar tment of Biology,

Da i i ch i C o l l e g e 9._[ P h a r m a c e u t i c a l S c i e n c e s , Fukuoka 815, and 2Department. o f Biology,

F a c u l t y o f Sc i ence , Kyushu U n i v e r s i t y , Fukuoka 812, Japan.

Four processes of stimulation-induced increase in t ransmit ter release have been known at the frog

neuromuscular junction (NMJ). We reported last year that two slower processes, augmentation and po- + + + +

tentiation, occur independently of internal Ca , by making use of the NMJ loaded with a Ca -chelator

BAPTA (Tanabe and Kijima, Neurosci. Lett. 99, 147, 19891. Among two other faster processes, the fast

facil i tat ion was completely lost at the BAPTA-loaded NMJ, while magnitude of the slow facil i tat ion was

unchanged and its decaying time constant was a l i t t le increased, compared with the normal NMJ. The + +

augmentation and potentiation of MEPP frequency observed under external Ca -free conditions (+EGTA

1 raM) were also l i t t le changed at the BAPTA-loaded NMJ. Three slower stimulation-induced increases of

t ransmit ter release were strongly suggested to be caused independently of the internal Ca ++ at the

releasing site. Dual release-regulating systems may exist at the NMJ, as well as in the mast cell.