Effects of neurotransmitters or drugs on the in vivo release of dopamine and its metabolites

The effects of neurotransmitters or drugs on the release of endogenous dopamine (DA) and extracellular levels of its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were examined in vivo by intracerebral dialysis. A dialysis tube was implanted stereotaxically through bilateral caudate nuclei of rats and perfused with the Ringer solution. Amounts of DA, DOPAC and HVA in the perfusates were measured by high performance liquid chromatography (HPLC) with electrochemical detection. The basal level of DA was 2.76 +/- 0.64 pg/min, whereas the levels of DOPAC and HVA were 218.7 +/- 20.7 and 142.4 +/- 10.6 pg/min, respectively. Apomorphine (4 mg/kg, i.v.) reduced the efflux of DA and its metabolites. Haloperidol (0.4 mg/kg, i.v.) did not change DA release and produced only a minor increase of its metabolites. This increase of metabolites was inhibited by pargyline. Met-enkephalin (10(-4) M), substance P (10(-4) M) and acetylcholine chloride (10(-4) M) added to the perfusing medium increased the release of DA. Met-enkephalin also increased the release of DOPAC. gamma-Amino-n-butyric acid (GABA, 10(-4) M) reduced the release of DOPAC and HVA when added to the perfusing medium. Thyrotropin releasing hormone (TRH, 5 mg/kg, i.v.) increased the release of HVA. These findings indicated that different mechanisms mediated effects of neurotransmitters or drugs on the release and metabolism of DA in the rat striatum.     

Affinity purification of a high molecular weight human breast cancer-associated antigen identified by the BCD-B4 monoclonal antibody

This study reports the purification and characterization of a high molecular weight human breast cancer-associated antigen identified by a previously described (1,2) murine monoclonal antibody, BCD-B4. Immunohistochemical analysis indicated that BCD-B4 recognizes an antigen expressed in an altered form on the human breast carcinoma cell line, BT-20, compared to the non-malignant human mammary epithelial cell line, HBL-100. Chemical treatments and enzymatic digestions suggested that the recognized moiety was a protein. The antigenic determinant was resistant to neuraminidase and periodate treatments but was sensitive to trypsin and proteinase K. The antigen was purified by affinity chromatography and its molecular weight, determined by SDS-PAGE analysis under non-reducing conditions, was proven to be 250 Kd. Under reducing conditions, the molecule dissociated into two polypeptides of 125 and 45 Kd, respectively. Both subunits could be isolated from normal HBL-100 and neoplastic BT-20 cellular protein extracts by affinity chromatography. The higher molecular weight subunit showed; however, qualitative and quantitative differences between the two cell lines: it was expressed in greater quantity on BT-20 cells and its molecular weight was 15 Kd higher. Both subunits could also be identified by immunoblots of BT-20 cells.     

Properties of neuronal activity related to a visual reaction time task in the monkey prefrontal cortex

1. Quantitative properties of neuronal activity related to a visual reaction time task were studied in the monkey prefrontal cortex. The task consisted of an initial waiting phase (3.0-s period), a warning phase (green lamp, a variable period of 1.5-3.5 s), a go phase (red lamp), and a reward phase. 2. A total of 189 task-related neurons showed 233 changes in discharge rates during the warning (n = 86), GO (n = 103), and reward (n = 44) phases of the task. Most of the task-related neurons (145/189, 77%) showed changes during only one of the task phases, and were designated W (warning phase)-type (n = 42), GO (go phase)-type (n = 59), and RE (reward phase)-type (n = 44) neurons. The remainder (n = 44, 23%) showed changes during both the warning and the go phases, and were designated WG (warning and go phase)-type neurons. In each phase, onset latencies, peak latencies, and decay times of each change were measured and compared. 3. The changes during the warning phase (n = 86) were separated into three groups based on decay time; that is, phasic changes (n = 31), phasic-tonic changes (n = 23), and tonic changes (n = 32). Onset latencies and peak latencies were homogeneously distributed, and there were no clear groupings, although phasic and phasic-tonic changes tended to show shorter latencies than tonic changes. 4. The changes during the go phase (n = 103) did not show distinct differences, either in terms of decay time or of latency. The changes during the go phase showed various degrees of coupling to both the visual go signal (GS) and lever-release hand movement. To quantitate the coupling, a value to indicate the degrees of coupling (coupling index) was calculated. The changes coupled more strongly to the GS (cue coupled), those coupled more closely to the lever release (movement coupled), and intermediate changes could be distinguished from each other. The cue-coupled changes showed shorter latencies from the time onset of the GS than the movement-coupled changes, and the intermediate changes showed intermediate latencies. The decay time and the duration of the intermediate changes were longer than those of the cue-coupled changes and the movement-coupled changes. 5. The properties of WG-type neurons were compared with those of W-type and GO-type neurons.(ABSTRACT TRUNCATED AT 400 WORDS)