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At least 487 records · Page 27Linked to original sources
PubMed1987

Heterogeneity of muscarinic receptors coupled to phosphoinositide breakdown in guinea pig brain and peripheral tissues.

Muscarinic receptors coupled to phosphoinositide hydrolysis (PI) are present in guinea pig bladder and colon. Compared to rat cerebral cortex, an extensively studied muscarinic/PI turnover system, all agonists were more potent and efficacious in both bladder and colon. The "M1-selective antagonists", pirenzepine and dicyclomine, were much more potent (Ki = 1-5 nM) and selective (300 to 500-fold) at both rat and guinea pig brain and guinea pig colon receptors, compared to PI-coupled receptors in guinea pig bladder. In contrast, "M2-selective antagonists", AF-DX 116 and HHSiD, were 2-6 fold more potent in bladder than in brain, while HHSiD was very potent in the colon (50 times more potent than in brain). These results suggest a pharmacological heterogeneity of PI-linked muscarinic receptors. If muscarinic receptors with a low affinity for pirenzepine are defined as M2, these results show that the guinea pig bladder contains PI-linked M2 muscarinic receptors, whereas the guinea pig colon contains PI-linked M1 receptors.

Animals↗
PubMed1993

Effects of diet-induced hyperthreoninemia. I). Amino acid levels in the central nervous system and peripheral tissues.

Rats were fed four levels of threonine (Thr, 0.4, 0.6, 0.8, and 5.8 g/100 g diet). After two weeks, Thr, serine (Ser), and glycine (Gly) levels were measured in plasma, liver, muscle, and central nervous system. The diet containing 5.8 g/100 g of Thr elevated Thr and Gly concentrations in plasma and nervous tissue in comparison with a standard diet. In muscle and liver, Thr concentrations were also raised but Gly levels did not change. The hepatic Thr dehydratase activity was enhanced. Diets containing moderate Thr quantities (0.6 and 0.8 g/100 g) induced slight elevations of Thr levels in all tissues. Gly concentrations were not modified. The activity of hepatic Thr dehydratase was diminished. Our results show that a high dietary content of Thr (15 times the normal levels) elevates Gly levels in various tissues, including the brain. On the contrary, diets containing 2 to 4 times the normal levels of Thr induce a weak hyperthreoninemia insufficient to modify brain Gly.

Alcohol Oxidoreductases↗
PubMedDate not supplied

Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation.

Studies using [3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by cortisol (10(-6) M) and inhibited by endogenous 5 alpha-reduced androgens: 5 alpha-androstene-dione greater than androsterone greater than dihydrotestosterone greater than epiandrosterone greater than 3 alpha- and 3 beta- androstanediol. It was also shown that 19-nortestosterone and 19-norandrostenedione (10(-6) M) inhibited E1 formation by 80%. Progesterone (10(-6) M) had no effect on aromatase activity, while the progestational agent R5020 (10(-6) M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action.

Aromatase↗
PubMed1986

Oxygen regimen in the human peripheral tissue during space flights.

A survey of the results of the experiment "Oxygen," carried out within the scope of the INTER-KOSMOS program in members of the permanent crews and of international visiting expeditions to the Soviet orbital station Salyut-6, is given. During the 7-day space flights of the international visiting expeditions a significant decrease in pO2ic by 3.28 kPa was observed. Local oxygen utilization reduced significantly by 0.44 kPa. During hyperventilation testing after return to earth a statistically significant decrease in the peak value by 1.39 kPa was noted. In the long-term crews of the orbital station Salyut-6 the highest decrease in pO2ic of 3.8 kPa and the absolutely lowest value of 3.4 -/+ 0.5 kPa during space flight were observed. The decrease in local oxygen utilization during the flight of 0.8 kPa/min was greater than that of the visiting crews. The results indicate the importance of investigating the dynamics of the oxygen regimen for medical control of the crew members both during the space flight and during the readaptation phase after return to earth.

Adaptation, Physiological↗
PubMed1988

Quantitation of N-acetyl-aspartyl-glutamate in microdissected rat brain nuclei and peripheral tissues: findings with a novel liquid phase radioimmunoassay.

Antibodies were raised in rabbits against the neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) coupled to bovine serum albumin via a carbodiimide linkage. One of these rabbit antisera, which preferentially recognizes coupled NAAG-like immunoreactivity (LIR), has been previously used to immunocytochemically localize NAAG-LIR. We have now employed a second of these antisera, which preferentially recognizes free NAAG, to develop a competitive liquid phase radioimmunoassay (RIA). Using this assay, we were able to detect picomole amounts of NAAG in rat tissue extracts. The specificity of the assay revealed a 60-fold greater affinity of the antibody for NAAG over N-acetyl-aspartate (NAA) and greater than one million-fold specificity for NAAG over both aspartate and glutamate. High-pressure liquid chromatographic (HPLC) separation of tissue extracts yielded only two detectable peaks of NAAG-LIR in collected fractions and these co-chromatographed with NAAG and NAA. NAAG levels determined by this liquid phase RIA and by HPLC were essentially identical after correction for the presence of NAA crossreactivity. The antibody that preferentially recognizes coupled NAAG was used to immunocytochemically localize NAAG-LIR to the red nucleus, the facial nucleus, the dorsal raphe, and the locus coeruleus. To further confirm this localization of NAAG, these and other nuclei were microdissected and levels of NAAG were determined by liquid phase RIA. Nuclei which stained intensely were found to contain high levels of NAAG by RIA and between 60 and 100% of this NAAG-LIR co-chromatographed with NAAG. These results support our previous conclusion that NAAG is co-localized in noradrenergic, serotonergic and cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The substance P content of peripheral tissues in several mammals.

Levels of substance P immunoreactivity (SPI) were determined in several skin and mucosal areas, in parts of the sympathetic nervous system, the urinary, biliary and respiratory systems of cats, rabbits and guinea-pigs, and in various skin and mucosal areas of humans by radioimmunoassay. Salient findings are (1) The general distribution pattern of SPI in rabbits was similar to that in rodents. (2) The highest SPI tissue levels were found in the sympathetic nervous system, notably in guinea-pigs. (3) The guinea-pig also had the highest SPI levels in ureter, urinary bladder and bile duct. (4) The aorta, pulmonary artery and portal vein of the rabbit contained very low amounts of SPI, the concentration in the carotid sinus being several fold higher. (5) Skin SPI content was generally highest in the cat, especially in the hindpaw-pad, and lowest in abdominal and back skin. (6) SPI levels found in postmortem human skin and mucosal samples are comparable to those found in other mammals. The observations are discussed in view of the sensory innervation of the various tissues.

Adult↗
PubMed1991

Peripheral tissue energy metabolism during recovery from hypothermia after cardiopulmonary bypass: effect of amino-acid infusions.

We studied the effects of amino-acid administration on the leg exchange of energy substrates and amino-acids during recovery from hypothermia after open heart surgery. Glucose (G, n = 5), glucose and conventional amino-acids (CA, n = 5) or glucose and branched chain amino-acids (BC, n = 5) were infused during recovery from hypothermia after open heart surgery. The leg exchange of energy substrates and amino-acids were measured after arrival at the intensive care unit, after rewarming, and 2h and 4h after rewarming during increasing amino-acid intake. Despite a normal stress response to surgery, reflected by increased energy expenditure and increased concentrations of insulin and catabolic hormones, amino-acids had no effect on the leg exchange of branched chain amino-acids, glutamine, alanine and energy substrates. This suggests that the transport of amino-acids and energy substrates into the cell are impaired after hypothermic cardiopulmonary bypass and intracellular substrates are utilised for the increased demand for energy during rewarming.

Journal Article↗
PubMed1986

Effects of neonatal methylmercury exposure on adrenergic receptor binding sites in peripheral tissues of the developing rat.

Neonatal exposure to methylmercury produces changes in patterns of tissue growth and function, in part, due to alterations in adrenergic neuronal input. To explore the mechanisms by which these changes come about, newborn rats were exposed to methylmercury (1 or 2.5 mg/kg per day) throughout the preweaning stage and the ontogeny of adrenergic receptor binding sites evaluated in liver, kidney, heart and lung, using [3H]prazosin (alpha 1-receptors), [3H]rauwolscine (alpha 2-receptors) and [125I]pindolol (beta-receptors). In the kidney, methylmercury caused decreases in beta- and alpha 1-receptor binding and increases in alpha 2-binding; previous work has shown that beta-receptor-mediated responses are generally enhanced in methylmercury-exposed pups, and the down-regulation of beta-receptor binding thus probably represents a compensatory action secondary to alterations in post-receptor coupling mechanisms. The effects of methylmercury on hepatic adrenergic receptors were different from those seen in the kidney, with substantial elevations in beta- and alpha 1-receptor binding apparent in the preweaning stage; this agrees also with the differences in effects of the mercurial on trophic reactivity and growth in the 2 tissues. Despite the fact that methylmercury causes activation of neonatal cardiac sympathetic nerves, beta-receptor binding sites in the heart were unaffected by methylmercury exposure; the failure to down-regulate cardiac postsynaptic receptors in the face of increased nerve activity again represents an anomaly of synaptic regulatory function. These results indicate that methylmercury alters adrenergic responsiveness, in part, through actions on the development of receptor binding sites, and further, that the organ-specificity and receptor subtype-selectivity are consistent with subsequent effects of the organomercurial on adrenergic participation in target organ growth; however, changes in receptor binding alone do not account for all of the effects of methylmercury on synaptic activity or trophic responses.

Aging↗
PubMed1984

Long term alterations in the excitability of the flexion reflex produced by peripheral tissue injury in the chronic decerebrate rat.

Chronic decerebrate rats have been prepared by the aspiration of all the cranial contents rostral to the mesencephalon. With careful nursing, body temperature control and orogastric tube feeding the rats survive for up to 4 months. The decerebrate rats have intact brain stem and spinal reflexes including locomotion, righting reflexes and grooming. Mild noxious cutaneous thermal and mechanical stimuli of an intensity which does not produce tissue damage evokes flexion withdrawal reflexes, vocalization, orientation to the site of the injury and generalized escape or attack responses, from the animals. These effects are transient and only occur during the application of the stimulus. The rats do not exhibit stress reactions, aggression or vocalization when handled before or after application of such noxious stimuli. The production of localized tissue injury by thermal or chemical means results in long term alterations (up to 6 weeks) in the thresholds and excitability of the flexor reflex, both ipsilateral and contralateral, to the site of the injury. It is proposed that the reduction in the flexor reflex threshold is analogous to the hyperalgesia and allodynia that follows tissue injury in man and that the long term alterations in the flexor reflex in the chronic decerebrate rat provide a model for the study of chronic pain, without the ethical problems associated with such studies in intact animals.

Afferent Pathways↗
PubMed1989

Cutaneous hypersensitivity following peripheral tissue damage in newborn infants and its reversal with topical anaesthesia.

The flexion reflex threshold has been used as a measure of sensation in a group of premature infants born at 27-32 weeks postmenstrual age. The threshold in an area of local tissue damage created by routine heel lances was half the threshold on the intact heel on the other side. This indicated a hypersensitivity to tissue damage analogous to tenderness or hyperalgesia reported in adults. In a double-blind study, treatment of the damaged area with the topical anaesthetic cream, EMLA, was found to reverse this hypersensitivity or in other words increase the flexion reflex threshold. Treatment with placebo had no effect. The results show that the newborn infant central nervous system is capable of mounting a chronic pain response to local injury which can be reduced by local anaesthetic.

Anesthetics, Local↗