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Volume 117 (2001)
- Issue 6 Pages 377-
- Issue 5 Pages 319-
- Issue 4 Pages 243-
- Issue 3 Pages 159-
- Issue 2 Pages 105-
- Issue 1 Pages 5-
Volume 117, Issue 3
Displaying 1-6 of 6 articles from this issue
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Award Lecture
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Masashi KATSURAArticle type: Others
Subject area: Others
2001 Volume 117 Issue 3 Pages 159-168
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSMechanisms for formation of drug dependence and emergence of withdrawal syndrome are not yet fully understood despite of a huge accumulation of experimental and clinical data. Several clinical features of withdrawal syndrome are considered to be common (i.e., anxiety) among patients with drug dependence induced by different drugs of abuse. In this review, we have discussed the possibility of the functional involvement of diazepam binding inhibitor (DBI), an endogeneous neuropeptide for benzodiazepine receptors with endogenously anxiogenic potential, in the development of drug dependence and emergence of its withdrawal symptom. The levels of DBI protein and its mRNA significantly increased in the brain derived from mice dependent on alcohol (ethanol), nicotine and morphine, and abrupt cessation of these drugs facilitated further increase in DBI expression. In the cases of nicotine- and morphine-dependent mice, concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase in DBI expression. Therefore, these alterations in DBI expression have a close relationship with formation of drug dependence and/or emergence of withdrawal syndrome and are considered to be a common biochemical process in drug dependence induced by different drugs of abuse.View full abstractDownload PDF (1440K) -
Yukihiro NODAArticle type: Others
Subject area: Others
2001 Volume 117 Issue 3 Pages 169-176
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSWe examined possible mechanisms in the development of latent learning by methods of behavioral pharmacology and confirmed them by using mutant mice. Mice that received dopamine agonists, a noradrenergic neurotoxin or a traumatic brain injury showed impairment of latent learning. This impairment was suggested to be mediated by imbalance of dopaminergic and noradrenergic systems since the impairment was attenuated by a noradrenaline uptake inhibitor or a dopamine-D2 antagonist. The heterozygous mice for the tyrosine hydroxylase (TH) gene and for the cyclic AMP (cAMP) response element binding protein (CREB) binding protein (CBP) gene showed impairment of latent learning in the water finding task. The spatial learning and hippocampal long-term potentiation (LTP) were normal in both the mutants. TH heterozygous mice showed a reduction of high K+-evoked noradrenaline release in the frontal cortex by the microdialysis technique and a reduction of cAMP of the brain cAMP content. The central noradrenergic systems and/or cAMP signal pathways play an important role in latent learning, but not spatial memory. In contrast with TH and CBP mutant mice, nociceptin-knockout mice showed an enhanced retention of latent learning in the water finding task, greater learning ability in the water maze task and larger LTP than wild-type mice. Such mice showed hyperfunction of dopaminergic systems in the cortex. Nociceptin itself induced latent learning impairment in wild-type mice. These results suggest that the nociceptin system seems to play negative roles in learning and memory. In conclusion, the results of mutant mice further supported our previous results of behavioral pharmacology and suggest that the alternation of catecholamine biosynthesis and cAMP signal pathways may play a key role in development of latent learning. They further suggest that the expression of genes mediated by phosphorylated CREB may be involved in the development of latent learning.View full abstractDownload PDF (896K) -
Takashi SEKINEArticle type: Others
Subject area: Others
2001 Volume 117 Issue 3 Pages 177-186
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSThe multispecific organic anion transporters have been indicated to be involved in the transmembrane transport of various anionic substances. The kidney and liver possess the distinct organic anion transport pathways for the elimination of potentially toxic anionic drugs and metabolites. In the kidney, proximal tubular cells actively excrete organic anions of both endogenous and exogenous origin. We have isolated the renal multispecific organic anion transporter, OAT1 (organic anion transporter 1), from the rat kidney. OAT1 is a 551-amino acid residue protein with 12 putative membrane spanning domains. OAT1 mediates sodium-independent, anion exchange for a variety of organic anions including p-aminohippurate, cyclic nucleotides, prostanoides, dicarboxylates, and anionic drugs including β-lactams, non-steroidal antiinflammatory drugs, diuretics and antiviral drugs. So far, three other isoforms have been identified. OATs comprise a new family of multispecific organic anion transporter, i.e., the OAT family. OATs show weak structural similarity to organic cation transporters (OCTs) and OCTN/carnitine transporters. All of the members of the OAT family are commonly expressed in the kidney, suggesting its significance in the renal organic anion excretion. In addition, OAT members appear to be responsible for the distribution/elimination of water solubule anionic drugs into/from the liver, brain and fetus.View full abstractDownload PDF (940K)
Reviews
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Shigetoshi CHIBASubject area: Others
2001 Volume 117 Issue 3 Pages 187-194
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSDouble-peaked vasoconstrictor responses to periarterial nerve electrical stimulation (PNS) were readily induced in the condition of 30-s trains of pulses in isolated, perfused canine splenic artery, using the cannula insertion technique. P2X purinoceptors have been shown to be involved mainly in the 1st peaked response and α1 adrenoceptors mostly in the 2nd one. Administrated NPY induced no direct vasoconstriction or only a slight vasoconstriction, and it inhibited the double-peaked vasoconstriction in a dose-related manner. A small dose of NPY Y1-receptor agonist, L-P NPY, readily potentiated the 2nd peaked response to PNS, and an increasing dose of LP-NPY did both the 1st and 2nd peaked responses. The 2nd peaked response was significantly inhibited by treatment with chloroethylclonidine (CEC), an α1B-adrenoceptor antagonist, but the 1st peaked response was not influenced. On the other hand, an α1A-antagonist, WB4101, rather potentiated the 2nd peaked response, although it did not modify the 1st one. Administered NA-induced constrictions were consistently inhibited by WB4101 but not by CEC. From these results, it is concluded that NPY inhibits the release of ATP and NA from periarterial nerve terminals by activation of presynaptic NPY Y2 receptors, and it potentiates PNS-induced vasoconstrictions via α1B-adrenoceptors by activation of postjunctional NPY Y1 receptors in the canine splenic artery.View full abstractDownload PDF (1381K) -
Shogo TOKUYAMA, Masakatsu TAKAHASHISubject area: Others
2001 Volume 117 Issue 3 Pages 195-201
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSPharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants were summarized. Analgesic effects of opioids, such as morphine and U-50, 488H, were blocked by ginseng in a non-opioid dependent manner. Furthermore, ginseng inhibited the tolerance to and dependence on morphine, and prevented the supressive effect on the development of morphine tolerance caused by coexposure to foot-shock stress, but not psychological stress. On the other hand, behavioral sensitization (reverse tolerance to ambulation-accelerating effect) to morphine, methamphetamine (MAP) and cocaine was also inhibited by ginseng. Interestingly, ginseng also inhibited the appearance of the recurrent phenomenon (reappearance of the sensitized state was observed at the time of readministration of MAP and cocaine even after a 30-day discontinuation of drug administration) of the effect of MAP and cocaine. The conditioned place preference of MAP and cocaine was completely blocked by ginseng. These findings provide evidence that ginseng may be useful clinically for the prevention of abuse and dependence of opioids and psychostimulants.View full abstractDownload PDF (991K)
Technical Note
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Hikaru TANAKA, Koki SHIGENOBUArticle type: Others
Subject area: Others
2001 Volume 117 Issue 3 Pages 203-210
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSIsolated atrial tissue preparations provide convenient models for studying drug effects on the myocardium. However, there are several points we must be aware of. Interventions which change the beating rate also affect contractile force (Starling’s Law). The membrane currents involved in the action potential as well as the excitation-contraction mechanisms differ between the atria and ventricle. Some membrane currents present only in the sino-atrial node and atrial myocardium may provide targets for novel bradycardiac agents and anti-atrial fibrillatory agents, respectively. The atrial tissue contains non-myocardial cells such as autonomic neurons and endocardial endothelial cells, which may be involved in the responses to various pharmacological stimuli.View full abstractDownload PDF (614K)
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