Search PubMed⌕ Search

Biomedical subjects

I Kitchen

Publications and source records attributed to I Kitchen.

101 records · Page 6Linked to original sources
PubMed1980

Effects of adrenalectomy and hypophysectomy on enkephalin content of the rat hypothalamus.

1 Hypothalamic content of enkephalin in rats has been measured by bioassay against methionine-enkephalin on field-stimulated mouse vas deferens after acid extraction and purification using Amberlite XAD-2 resin.2 Surgical stress lowered hypothalamic enkephalin content initially but 6 days after operation the content was higher in sham-operated than in adrenalectomized animals.3 Corticosteroid replacement therapy showed that hypothalamic enkephalin content was not related directly to circulating corticosteroid levels and that it was increased by the stress of handling and injection.4 Hypothalamic enkephalin content of rats that had undergone hypophysectomy 11 days earlier did not differ from that of intact animals but surgical stress, which lowered content in intact rats and had no effect after adrenalectomy, produced a rise in content in these hypophysectomized animals.5 The ingestion of 0.9% saline, in place of water, by sham-adrenalectomized rats altered the effect of surgical stress on hypothalamic enkephalin content without affecting the resting levels.6 Of extracts from adrenalectomized rats, 10% contained a substance that behaved atypically on the mouse vas deferens, showing a slower onset and offset of action. The mol. wt. of the substance and sensitivity to naloxone reversal appeared to be similar to enkephalin, but it was resistant to carboxypeptidase-A and protease treatment.7 It is concluded that the enkephalin content of the hypothalamus is affected by activity in the hypothalamus-pituitary-adrenal system but that it is not related in a simple manner to the levels of corticotrophin releasing hormone, corticotrophin or corticosteroids.

Adrenal Cortex Hormones↗
PubMed1979

Different effects of current strength on inhibitory responses of the mouse vas deferens to methionine- and leucine-enkephalin.

The inhibitory potency of methionine (Met)-enkephalin on the field-stimulated mouse vas deferens was greatly increased by a reduction in current strength whilst that of leucine (Leu)-enkephalin increased only slightly. All currents were submaximal and all muscle twitches were neuronally evoked. These results suggest that inhibitory effects of Met- and Leu-enkephalin in the mouse vas deferens are not commonly mediated and provide a rapid method for ascertaining heterogeneity of enkephalin extracts.

Animals↗
PubMed1979

Interindividual and interspecies variation in the metabolism of the hallucinogen 4-methoxyamphetamine.

1. The qualitative and quantitative aspects of the urinary elimination of orally administered 4-methoxy[14C]amphetamine have been examined in the rat and guinea-pig and in three volunteer human subjects, to determine interspecies and interindividual variations in disposition of the drug. 2. Both rat and guinea-pig excreted 70--80% of the administered dose(6 mg/kg) in the urine within 24 h, mainly as metabolites. 3. In the guinea-pig, the drug was metabolized by O-demethylation to give 4-hydroxyamphetamine, which was excreted free (4% dose) and conjugated (73%). No other metabolite was detected. 4. The rat metabolizes the drug both by O-dealkylation and by side-chain oxidation, the products being 4-hydroxyamphetamine (5% of dose free and 60% conjugated) and 1-(4'-methoxyphenyl)propan-2-one oxime (5% dose, free and conjugated). 5. In man the drug (dose 5 mg) is metabolized by O-demethylation and by side-chain oxidation. Marked intersubject variations were observed both in the array and quantitative aspects of metabolite excretion. Two subjects excreted mainly 4-hydroxyamphetamine (free and conjugated) together with smaller amounts of 1-(4'-methoxyphenyl)propan-2-one oxime and 4-hydroxynorephedrine. The third subject, however, who was previously known to exhibit a genetically determined defect in drug oxidation, was defective in O-dealkylation of 4-methoxyamphetamine, and the main excretion products were the unchanged drug together with products of side-chain oxidation, namely, 1-(4'-methoxyphenyl)propan-2-one oxime, 1-(4'-methoxyphenyl)propan-2-one and 4-methoxybenzoic acid. 6. Inter-individual differences in oxidative O-demethylation of the drug are discussed in relation to current theories on the aetiology of schizophrenia and reported fatalities arising from abuse of the drug.

Adult↗
PubMed1975

Enzyme potentiated hyposensitization: IV. effect of protamine on the immunological behavior of beta glucuronidase in mice and patients with hay fever.

The ability of beta glucuronidase and a small dose of antigen to modify the anaphylactic reaction of previously sensitized mice has been further investigated. Protamine has an important effect on the immunological behavior of the enzyme. A trial on hay fever patients shows that the results in mice are relevant and that the method can produce significant clinical hyposensitization.

Animals↗
PubMedDate not supplied

Developmental modulation of cysteine conjugate beta-lyase/glutamine transaminase K/kynurenine aminotransferase mRNA in rat brain.

Cysteine conjugate beta-lyase/glutamine transaminase K/kynurenine aminotransferase (CS-lyase/GTK/KAT) is a tri-functional enzyme found in several organs, including the brain. Kynurenine aminotransferase is important in tryptophan metabolism in the CNS, producing kynurenic acid, a NMDA receptor antagonist and neuroprotective. Tryptophan not metabolised via kynurenine aminotransferase may form quinolinic acid, a NMDA receptor agonist and neurotoxin. Kynurenic acid co-treatment blocks quinolinic acid induced lesions in the CNS in rat. In many conditions exhibiting neurodegeneration (i.e. Huntington's, Parkinsonism, Down's syndrome) quinolinic acid and/or kynurenic acid concentrations are altered, suggesting the ratio of these chemicals may be important in neurodegeneration. We have investigated the developmental modulation of CS-lyase/GTK/KAT mRNA in rat brain. CS-lyase/GTK/KAT mRNA was measured in 14, 21, 28, 35, 42 day post-natal and adult rats. While many regions demonstrated a steady increase to adult levels, two other profiles were seen. Five regions rapidly reached adult levels of the mRNA, while two peaked above the adult level before falling back. This provides evidence that expression of the CS-lyase/GTK/KAT gene is physiologically modulated, and provides the basis for further investigation into the mechanism of control. Artificial modulation could possibly be used to alter levels of the neuroprotectant kynurenic acid in neurodegeneration.

Animals↗
PubMedDate not supplied

Bombesin-induced behavior in infant rats.

The behavioral effects of bombesin in 5-, 10- and 20-day-old rat pups have been investigated and the peptide was found to induce scratching (1, 10 mg/kg IP) and grooming (10 mg/kg IP) as early as 5 days after birth. Bombesin did not produce any other overt activities in the developing pups in doses of up to 10 mg/kg, however, lower doses of the peptide (0.1, 1 mg/kg IP) reduced intake of a wet mash diet in deprived 15-day-old rat pups resulting in significant decreases in body weight compared with control animals. These behavioral responses agree with the well-documented effects of bombesin in adult rats and are also in accordance with results from biochemical studies which have shown the existence of receptors for bombesin-like peptides in the rat central nervous system from an early age.

Aging↗
PubMedDate not supplied

Interactions between anticholinesterase poisoning and opioid analgesia and locomotion in mice.

Interactions between anticholinesterases and opioid drugs on antinociception and locomotor behaviour have been studied in the mouse. The anticholinesterase di-isopropylfluorophosphate (DFP) (1 mg/kg), pyridostigmine (1 mg/kg) and neostigmine (200 micrograms/kg) or drugs used to treat anticholinesterase poisoning (atropine, pralidoxime and diazepam) were not antinociceptive. DFP, at doses which produced marked neurotoxicity (2 mg/kg), produced antinociception which was not mediated by opioid receptors. The antinociceptive effects of alfentanil, but not fentanyl or morphine, were potentiated by DFP, whereas pyridostigmine and neostigmine were without effect. The potentiating activity of DFP was unaffected by atropine, pralidoxime and diazepam. DFP (1 mg/kg) produced a small degree of hypolocomotion whilst atropine and pralidoxime produced marked hyperlocomotion. Diazepam alone and with DFP, atropine, pralidoxime or opioid drugs produced marked motor incapacitation. Hyperlocomotion induced by morphine and alfentanil was reduced by DFP but fentanyl hyperlocomotion was unaffected. Treatment of DFP toxicity with atropine and pralidoxime reversed the effects on alfentanil locomotion but failed to alter DFP's action upon morphine or fentanyl locomotion. Atropine and pralidoxime treatment alone did not affect fentanyl hyperlocomotion, attenuated alfentanil hyperlocomotion and produced marked hypolocomotion in morphine-treated mice. Opioids and anticholinesterases do not exhibit common interactions and their effects are dependent on both opioid, anticholinesterase and the behaviour studied.

Alfentanil↗
PubMedDate not supplied

Lead toxicity and alterations in opioid systems.

The opioid peptide system in the brain is probably the most extensive and diverse peptidergic transmission system. Three peptide precursors, pro-opiomelanocortin, proenkephalin and prodynorphin produce over 20 opioid peptides collectively known as the endorphins, enkephalins and dynorphins. Their effects are mediated by three receptors mu, delta and kappa, and the opioid system has control over several physiological functions including pain, locomotion, mood, diuresis, thermoregulation, stress, respiratory, gastrointestinal and cardiovascular function. Lead treatment (primarily using rat models) has shown that exposure to this metal in the perinatal period alters the development of endorphins and enkephalins, toxic effects which for the pro-opiomelanocortin products may be manifested at the gene level. Lead also alters the development of mu and delta receptors and biological responses to opioids such as analgesia, locomotion and stress responses. There are indications that the dynorphin/kappa opioid system is less affected than the mu and delta systems and this may suggest vulnerability to toxicity in the postnatal period as kappa systems are fully developed at birth whilst mu and delta systems are immature. In addition, hypothalamic and pituitary disruption of opioid peptides, plus alteration of stress-mediated activity by lead point to toxicity upon opioid controlled hormonal function. Comparative studies with other CNS neurochemicals and measures of blood lead levels suggest that opioid peptides are among the most sensitive neurotransmitter/neurohormonal systems to toxic insult by lead.

Animals↗
PubMedDate not supplied

Effect of perinatal lead treatment on morphine dependence in the adult rat.

The effect of perinatal lead exposure (at 300 and 1000 ppm in the maternal drinking water from conception to postnatal day 14) on the opioid withdrawal syndrome in adult offspring has been studied to assess if lead produces long term disruption of opioid systems manifested as altered morphine dependence. Dependence was induced in 50 day old rats by administration of morphine in osmotic mini-pumps implanted subcutaneously and delivering 5, 15 or 40 mg/kg/day. At postnatal day 55 an opioid withdrawal syndrome was precipitated by administration of naloxone (4 mg/kg i.p) and withdrawal behaviour scored over the next 30 min. Both objective (jumping, weight loss, weight of excreta, wet dog shakes, mouthing and face washing) and subjective (teeth chatter, ptosis, diarrhoea, irritability) measures were scored. 60 min after naloxone animals were killed and plasma corticosterone measured as a biochemical index of withdrawal. Morphine withdrawal scores and plasma corticosterone exhibited a clear dose relationship and there were no significant differences between 0 and 300 ppm lead-exposed groups. However withdrawal scores in 1000 ppm lead-exposed animals were lower in 15 and 40 mg/kg morphine treated rats, predominantly associated with lower weight loss, wet dog shakes and mouthing responses. Paradoxically corticosterone levels were elevated in the 40 mg/kg morphine dose group. The results support other evidence that perinatal lead exposure can induce disruption in opioid functioning which persists to adulthood and suggest a possible link between lead and opioid addiction.

Animals↗