Progress in biochemical pharmacology最新文献

A brief overview of the reproductive capacities of both men and women in alcoholism is presented. A historical evaluation indicates a resurgence of interest in this area. The effect of chronic alcohol consumption on both male fertility and potency is reported in conjunction with alcohol-mediated effects on the female subject. Emphasis is placed on pharmacokinetics, metabolism and drinking behavior of the alcoholic female. The adverse actions of some therapeutic drugs and chronic alcohol consumption is discussed in relationship to fetal alcohol syndrome and the accompanied mental and somatic abnormalities.

The effects of ethanol ingestion during pregnancy on total folate levels in fetal tissues and on the concentrations of free amino acids in fetal and maternal plasma were examined in the rat. No differences were observed between the ethanol-fed and the control groups in total folates in fetal brain and liver. However, the concentration of fetal plasma histidine was reduced by 50% as a result of maternal ethanol consumption; the maternal plasma histidine level was not affected. It is suggested that fetal malnutrition in an essential amino acid, histidine, could impair fetal protein synthesis producing the fetal alcohol syndrome.

The in vivo effect of various agents, with different pharmacologic properties, on cytosolic EP-ALDH was studied in the rat. Injection of a large dose of PYZ inhibited EP-ALDH 16 h after the injection. Short-term administration of a moderate daily dosage of PYZ also inhibited endogenous EP-ALDH from saline controls. Semichronic administration of a small daily dosage of DIS resulted in inhibition of EP-ALDH. Short-term administration of drugs with various pharmacologic profile produced little change in the specific activity of EP-ALDH. This is compared with an induction and an inhibition of T-ALDH as a function of treatment with an antiandrogen and an estrogenic drug, respectively. The results show lack of response of EP-ALDH towards pharmacologic intervention which may imply certain specificity for EP-ALDH.

The subcellular distribution of the enzymes primarily involved in the metabolism of ethanol and acetaldehyde were made in the rat testis and in the epididymis. The enzymes measured were alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). They were NAD-dependent, temperature sensitive and displaying maximal activity in the presence of pyrophosphate buffer at pH 9.8. Both enzymes were readily measurable in the 10% (w/v) testicular and epididymal homogenates. The ADH activity was mainly localized in the nuclear and in the cytosolic fractions of the testis compared to the absence of measurable ADH activity in the epididymis. Testicular ALDH was measurable in all subcellular preparations, i.e. in the nuclear, in the mitochondrial, in the cytosolic and in the microsomal fractions. Maximal testicular ALDH activity was determined in both the nuclear and the cytosolic components compared to a lower microsomal ALDH activity. Determination of Km shows that cytosolic ALDH possesses the lowest apparent Km as contrasted with a high value for the mitochondrial ALDH. Testicular cytosolic ADH but not ALDH was noncompetitively inhibited by 3-methoxytyramine, histamine and d-amphetamine in vitro.

Several lines of evidence indicate that female sex steroids, especially estrogen, interact with ethanol pharmacokinetics. Both animal and human studies are consistent in indicating that voluntary intake of alcohol decreases with increasing estrogen concentrations. Such effects are equivocal with progesterone and nonexistent with testosterone. There is some suggestion that estrogen modulates monoamine oxidase activity and via that mechanism alters sympathetic nervous system tone. Alterations in sympathetic nervous system tone, in turn, can alter gastric motility and absorption of alcohol from stomach and intestines. Several types of studies, both animal and human, indicate that high estrogen concentrations also impair ethanol metabolism. At present the exact mechanism of action for this effect is not known. Future studies investigating this aspect are indicated. At present the effect of sex steroids on performance and its interaction with alcohol do not show a clear relationship. There are contrary pieces of information both for and against the view that menstrual cycle, performance and alcohol interact.

The uptake of (3H)dopamine into nerve endings (synaptosomes) isolated from cortex and brain stem of rats under various stages of ethanol intoxication were studied. Acute or chronic ethanol treatment inhibited the high affinity uptake of dopamine into both regions by about 30% when rats were still under ethanol. The inhibition in brain stem persisted even after 120 h of withdrawal from ethanol. In cortex, 16 h after acute treatment, the uptake was slightly (about 10%) elevated from that of control in contrast to chronic rats, which were 43 and 41% more than that of the control after withdrawal from ethanol for 48 and 120 h, respectively.