Electrophysiological studies using spectral analysis techniques were undertaken in rabbits to determine whether or not hippocampal rhythmical slow activity (RSA, theta wave activity) was affected by the 5-hydroxy-tryptamine1A (5-HT1A) agonists 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) and 3a alpha, 4 beta, 7 beta, 7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4, 7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate (SM-3997, a newly synthesized anxiolytic drug). Intravenous administration of 8-OH-DPAT and SM-3997 induced a desynchronized pattern with low-amplitude slow wave activity in the hippocampal EEG and inhibited RSA generation following stimulation of the midbrain reticular formation. RSA was also inhibited by 5-HT1A related anxiolytics such as buspirone, gepirone, and ipsapirone. The effects of 8-OH-DPAT and SM-3997 on the hippocampal RSA were blocked by pindolol, which has 5-HT1A antagonistic activity. Direct microinjection of these 5-HT1A selective agonists into the hippocampus inhibited generation of the hippocampal RSA. These findings indicated that 8-OH-DPAT and SM-3997 inhibited the hippocampal RSA by acting on hippocampal 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMedDate not supplied

Acceleration of actin polymerization and rapid microfilament reorganization in cultured hepatocytes by cyclochlorotin, a hepatotoxic cyclic peptide.

Cyclochlorotin (= chloropeptide, CC) is a hepatotoxic mycotoxin of Penicillium islandicum Sopp. The effect of CC on actin polymerization was examined by the measurement of changes in fluorescence intensity using pyrene-labeled actin and high shear viscosity. In the presence of CC, the time course of actin polymerization was accelerated in a dose dependent manner (2.5 ng/ml-2.5 microg/ml), without affecting the final level of viscosity. CC exerted a strong stabilizing effect on actin, enabling it to maintain its filamentous form in the presence of members of actin-binding proteins, including those of the gelsolin family prepared from hepatocytes. Microscopic observation revealed that in cultured hepatocytes, 1.0 microg/ml of CC induced bleb formation and changes in the microfilament. These observations indicated that after contact of the hepatocyte with CC, the following events were probable. The toxin passed through the cell membrane by a transport system and immediately reacted with the actin-actin binding proteins underlying the lipid bilayer. Bleb formation and hepatotoxicity were thus induced.

Actins↗

PubMedDate not supplied

Association of benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid (BPDE-DNA) adduct level with aging in male smokers and nonsmokers.

We used our new flow cytometric method to measure benzo[a]pyrene-diolepoxide-deoxyribonucleic acid adduct levels in peripheral lymphocytes from healthy male smokers and nonsmokers. Smokers who had pack-years of 20 or more had significantly higher mean benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct levels than nonsmokers. In smokers, the adduct levels were correlated significantly with age, years of smoking, and pack-years, whereas daily tobacco consumption was not correlated with adduct levels. We also found a positive relationship between age and benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct levels in nonsmokers. Passive exposure to tobacco smoke was not associated with adduct levels. The results of our study indicate that benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct levels may be closely related to aging and that tobacco smoking-as well as other environmental factors-may play a role in the benzo[a]pyrene-diol-epoxide-deoxyribonucleic acid adduct formation.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗