Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology最新文献

1. Glycerol treatment enhanced NADH- and NADPH-driven active oxygen formation and thiobarbituric acid reactive substances (TBARS) in the lungs of ddY mice treated with 4-nitroquinoline 1-oxide (4NQO). 2. A glycerol-associated effect on active oxygen formation and TBARS was not observed in the lungs of A/J mice treated with 4NQO. 3. The differences in the changes of active oxygen formation and TBARS by glycerol treatment between two strains was in agreement with the difference in the enhancing effect of glycerol on 4NQO-induced pulmonary tumorigenesis in mice. This indicates that the alteration in the levels of NADH- and NADPH-driven active oxygen formation and TBARS in the lungs could play a significant role in the enhancement of tumorigenesis associated with glycerol.

1. The values of both Kd and Bmax of [3H] dihydroalprenolol binding in the cerebral cortical membranes of old-aged (12 month old) SAM-P/1 were not significantly different compared with those of young (2 month old) SAM-P/1. 2. The values of Ki of metoprolol in the young and old aged SAM were 119 +/- 39.5 nM and 157 +/- 55 nM, respectively. 3. The values of beta 1/beta 2 ratio of the young and old aged SAM were 1.67 +/- 0.15 and 1.64 +/- 0.13, respectively. 4. These results suggest that there were no significant changes of binding characteristics of beta 1 and beta 2 adrenoceptors during aging in the cerebral cortex of SAM.

1. Drugs were administered to a suprachiasmatic nucleus through a chronically implanted cannula at the second day of a torpor bout of hibernating ground squirrels. After naltrexone injection, the body temperature of the hibernating animals increased and they aroused from hibernation within 20 hr after the injection. 2. Further experiments show that intra-suprachiasmatic nucleus perfusion of 1 nmol of ICI 174864 or nor-BNI, not beta-FNA, were able to increase the body temperature of hibernating ground squirrels and aroused them from hibernation within 20 hr after the injection.

1. Peptides C111 (Gly-Val-Tyr-Pro-His-Lys) and C112 (Ile-Arg-Pro-Val-Gln), extracted from the autolysis product of bonito liver and intestine, have been shown to inhibit angiotensin converting enzyme (ACE) activity in vitro with IC50s of 1.6 microM and 1.4 microM, respectively. We examined the effects of oral administration of these peptides on blood pressure. 2. Oral administration of these peptides (500 mg kg-1 body weight each) inhibited the pressor effect of intravenously administered angiotensin I in Sprague-Dawley rats. 3. In spontaneously hypertensive rats, oral administration of these peptides (100-200 mg kg-1 body weight) showed depressor effects. 4. These results suggest that the peptides, C111 and C112, are orally effective ACE inhibitors with hypotensive effect.

1. A closer characterization of the potassium channel opened by the application of dopamine (DA) on an identified Helix pomatia neuron was attempted. The effect of K+ channel blockers (TEA and 4-AP) on the DA-induced current was examined. The results indicate that the channel opened by DA does not share the pharmacological properties of other snail neuron K-channels. 2. The I-V relation for IDA was successfully fitted by the Constant Field equation except below the reversal potential where the current was smaller than expected. The assumption that DA binding is voltage-sensitive is supported by the increment of the Hill coefficient with hyperpolarization (from nH approximately equal to 1 to nH approximately equal to 2). 3. The presence of the phosphodiesterase inhibitor IBMX does not affect the DA induced outward current. However, the assumption that the snail neurons' DA receptor belongs to the D2 class is in contrast to the antagonistic effects of ergot alkaloids which, in mammalian neurons, are competitive antagonists of D1 receptors. 4. The examination of the voltage-sensitivity of the blocking action of the ergot alkaloid (Bromoergocryptinine) revealed that it does not compete with DA for the same binding site as in mammalian D1 receptors.

1. The acute effects of amiodarone, a powerful antiarrhythmic drug, on transient depolarizations (TDs) and/or triggered activity (TA) induced by an overdrive stimulation in the condition of low potassium (2.7 mM) and high calcium (5.4 mM) solution were evaluated on isolated ventricular papillary muscles from guinea pig, by means of conventional microelectrode techniques. 2. The amplitude of the induced TDs was enhanced by increase in stimulus number and frequency during overdrive stimulation, and the coupling interval of TDs was shortened. 3. Amiodarone (4.4 x 10(-5) M) significantly decreased the amplitude of TDs, and prolonged the coupling interval. 4. On the other hand, superfusion with a higher concentration (4.4 x 10(-4) M) of amiodarone tended to induce automatic activity. 5. Possible implications with respect to the antiarrhythmic activity of amiodarone are discussed.

1. Sphingosine inhibited the binding of [3H]quinuclidinyl benzilate (QNB), a potent and specific muscarinic antagonist, in dispersed rat parotid acinar cells. 2. The inhibition of [3H]QNB binding was expressed as decrease in affinity without significant change of a number of membrane sites. 3. The effect of sphingosine on the binding was not affected by the chelation of extracellular Ca2+. 4. H-7, an inhibitor of protein kinase C, failed to decrease [3H]QNB binding. 5. Stearylamine, an analogue of sphingosine, was as effective as sphingosine in inhibiting [3H]QNB binding. 6. These results suggest that sphingosine inhibits muscarinic cholinergic receptor binding by a mechanism that is independent on extracellular Ca2+ and protein kinase C.

1. The enzymatic, hemorrhagic, procoagulant and anticoagulant activities of venoms of some animals including snakes, lizards, toads, scorpions, spider, wasps, bees and ants were compared. 2. Snake venom was the richest source of enzymes among the animal venoms. Most other animal venoms were devoid of phosphodiesterase, L-amino acid oxidase, alkaline phosphomonoesterase and acetylcholinesterase activities and only a few exhibited arginine ester hydrolase activity. These venoms, however, exhibited wide ranges of protease, 5'-nucleotidase and hyaluronidase activities. Most of the animal venoms examined exhibited some phospholipase A activity. 3. Other than snake venoms, only venoms of the toad Bufo calamita and the lizards were hemorrhagic, and only venoms of the social wasps, social bees and harvester ant exhibited strong anticoagulant activity. Procoagulant activity occurs only in snake venoms.

1. Significant differences were observed between the hamster and the rat in terms of the secretion of fluid and protein from submandibular glands in response to pilocarpine, phenylephrine and isoproterenol. 2. In both the rat and the hamster the secretory responses induced by pilocarpine, phenylephrine and isoproterenol were inhibited by pretreatment with 4-DAMP, prazosin and metoprolol, respectively. 3. These results suggest that the submandibular glands of the hamster and the rat have M3-cholinoreceptors, as well as alpha 1- and beta 1-adrenoceptors, and that these receptors play different roles in the secretion of fluid and protein from hamster and rat submandibular glands.