Influence of repeated administration of desmethylimipramine on beta adrenergic and muscarinic cholinergic receptors and 45Ca++ binding to sarcoplasmic reticulum in the rat heart.
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Biomedical subjects
Publications and source records attributed to K Oki.
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The present experiment was designed to pharmacologically characterize receptors which mediate the clonidine-induced locomotor change in the developing rat. A subcutaneous injection of clonidine (0.78 mumol/kg) produced locomotor hyperactivity in 7-day-old rats but hypoactivity in 20-day-old rats. Phenoxybenzamine (1.5 mumol/kg, 5.9 mumol/kg and 15 mumol/kg) decreased spontaneous activity in a dose-dependent manner but did not antagonize clonidine-induced hypoactivity in 20-day-old rats. By contrast, the significant reversal of the clonidine-induced hypoactivity by pretreatment with phentolamine (1.6 mumol/kg and 6.3 mumol/kg), yohimbine (1.3 mumol/kg and 5.1 mumol/kg) and piperoxan (7.4 mumol/kg) was observed at such doses when the blockers did not cause any hypoactivity by themselves. It is suggested that clonidine could induce locomotor hypoactivity by activating presynaptic (alpha 2-type) alpha-adrenoceptors in the CNS of 20-day-old rat.
The behavioral effect of thyrotropin releasing hormone (TRH) was investigated in the developing rat pretreated with 6-OHDOPA at birth. An IP injection of TRH (20 mg/kg) increased walking with sniffing, rearing, body shaking, grooming, chewing and licking in the 7-, 14-, 20- and 30-day-old as well as in the adult rat. TRH-induced locomotor stimulation began a few minutes after the injection and lasted for approximately 60 min. But on Day 7, TRH produced locomotor stimulation betwen 1.5 hr and 3.5 hr after the injection. Neonatal treatment with 6-OHDOPA markedly potentiated TRH-induced locomotor stimulation and behavioral arousal in the 7-day-old rat but not in the 14-day-old and adult rat. The marked potentiation of TRH-induced locomotor stimulation by 6-OHDOPA in the 7-day-old rat was reduced by alpha-flupenthixol (pA2=5.9) and phenoxybenzamine (pA2=4.4). These results suggest that central dopamine neurons are involved in TRH-induced behavioral arousal in the infant rat.
The mesolimbic-striatal content of 3,4-dihydroxyphenylacetic acid (DOPAC) gradually increased with age in the developing rat. An intraperitoneal (i.p.) injection of apomorphine (2 mg/kg) or haloperidol (0.1 mg/kg) caused a significant change in the DOPAC content on day 20 and day 70, but not on day 7. However, a higher dose of apomorphine (10 mg/kg, i.p.) or haloperidol (5 mg/kg, i.p.) as well as that of alpha-flupenthixol (0.5 mg/kg, i.p.) significantly affected the mesolimbic-striatal content of DOPAC in 7-day-old rats. In 24-day-old rats subchronically treated with haloperidol (1 mg/kg to 10 mg/kg for 10 days, s.c.), apomorphine (2 mg/kg, i.p.) produced a significant reduction in the mesolimbic content of DOPAC at the withdrawal stage of the drug, but not in control rats. It is suggested that mesolimbic-striatal dopamine (DA) receptors which are not fully sensitive to DA agonists and antagonists on day 7 reach functional maturity by 20 days of the postnatal age in the rat.
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Fusion of red blood cells (RBC) induced by hemagglutinating virus of Japan (HVJ) has been studied using a phosphatidylcholine spin label. The spin label was readily incorporated and diffused into the lipid bilayer portion of the viral envelope. The exchange broadening in the electron spin resonance (ESR) spectrum of densely labeled virus disappeared rapidly when the virus was mixed with RBC at 37 degrees. The spectrum gradually approached that of the host cell spin labeled with the phosphatidylcholine label. The results directly indicate transfer and intermixing of phospholipid molecules between the viral envelope and RBC membrane. The transfer reaction was strongly dependent on temperature. No transfer was observed at lower temperatures where the virus adsorbed to the cell and caused aggregation but no hemolysis and fusion. The transfer rate remained negligibly small until 19 degrees and increased rapidly between 25 and 30 degrees. The virus-induced hemolysis showed similar temperature dependence. The transfer rate was greatly reduced under inhibitory conditions of fusion: glutaraldehyde treatment of RBC, trypsin treatment of HVJ, or the presence of concanavalin A. Only slight transfer was observed from fusion-inactive influenza virus to RBC. The transfer was greatly enhanced by the help of HVJ. The close parallelism suggests that the transfer and intermixing are necessary steps to the cell fusion. The transfer rate was dependent on fluidity of the host cell membrane and independent of the viral dose. The virus-induced transfer of phospholipid molecules between RBC's was also detected by the spin label. Its temperature dependence was quite similar to that for the virus-to-cell transfer. The intercellular transfer was nearly proportional to the viral dose.
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