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Biomedical subjects

J F Collins

Publications and source records attributed to J F Collins.

At least 163 records · Page 9Linked to original sources
PubMed1982

Isomers of 2-amino-7-phosphonoheptanoic acid as antagonists of neuronal excitants.

The D(-)-isomer of 2-amino-7-phosphonoheptanoic acid ( (-)APH) was active as an antagonist of N-methyl-D-aspartate (NMDA) excitation of central neurones. The L(+)-isomer was inactive. The antagonism was also selective, kainate and glutamate responses being relatively unaffected. Excitatory responses to ibotenic acid, a neurotoxic amino acid analogue, were less susceptible to blockade by (-)APH than NMDA, but more so than kainic acid. Ibotenate may therefore act partly on NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1982

Anion-dependent modulation of [3H]muscimol binding and of GABA-stimulated [3H]flunitrazepam binding by picrotoxin and related CNS convulsants.

Picrotoxin, isopropylbicyclophosphate (IPTBO) and related CNS-convulsants have allosteric effects on the binding of ligands to the GABA/benzodiazepine receptor complex. When binding experiments were performed at 23 degrees C and at 35 degrees C, these drugs inhibited [3H]muscimol binding and muscimol- or GABA-stimulated [3H]flunitrazepam binding, respectively. Both effects required the presence of C1-, Br-, I- but not of F- or SO4(2-). Picrotoxin and IPTBO could only partially inhibit [3H]muscimol binding. In contrast other GABA antagonists and convulsants like bicuculline, 3 alpha-hydroxy-16-imino-5 beta-17-aza-androstan-11-one (R 5135), strychnine and d-tubocurarine interferred completely with [3H]muscimol binding, also in the absence of those ions mentioned above which were essential for the effects of picrotoxin. Our results support the notion that drugs like picrotoxin and IPTBO which interfere with the GABA receptor effector system, may lead to an allosteric perturbation of GABA-recognition sites.

Animals↗
PubMed1982

Anticonvulsant action of excitatory amino acid antagonists.

Compounds that antagonize neuronal excitation induced by dicarboxylic amino acids were tested in two animal models of epilepsy, namely sound-induced seizures in DBA/2 mice and threshold pentylenetetrazol seizures in Swiss mice. Sound-induced seizures could be prevented by intracerebroventricular injection of compounds that block excitation due to N-methyl-D-aspartic acid. The most potent such compound, 2-amino-7-phosphonoheptanoic acid, was anticonvulsant in both test systems when given either intraperitoneally or intracerebroventricularly. Specific antagonists of excitation that is caused by amino acids provide a new class of anticonvulsant agents.

Amino Acids, Dicarboxylic↗
PubMed1982

Phosphonate analogues of acidic amino acids: inhibition of excitatory amino acid transmitter binding to cerebellar membranes and of the stimulation of cerebellar cyclic GMP levels.

An examination was made of the ability of phosphonate analogues of acidic amino acids to interact with excitatory amino acid receptors, employing binding assays for [3H]glutamate and [3H]aspartate and by investigating the inhibitory effects of these compounds on the stimulation of cerebellar cyclic GMP levels. In both systems the phosphonates exhibited inhibitory activity, although the cGMP system corresponded better with electrophysiological data. The higher homologues (e.g. 2-amino-5-phosphonovalerate) showed high selectivity for NMDA-type receptors and this effect was stereospecific, with the (-)-isomers being at least 4-7 times more active than the (+)-forms.

2-Amino-5-phosphonovalerate↗
PubMed1982

Response manipulation on the depression Adjective Check List.

Explored response manipulation on the Depression Adjective Check List (DACL) in a 2 (trials) x 3 (instructions to fake) x 2 (sex) x 2 (order) mixed factorial, counterbalanced design in which 240 college students, 120 males and 120 females, were assigned randomly to one of six conditions with 20 males and 20 females per condition. For conditions 1, 2, and 3, each session consisted of two trials. In trial 1, Ss completed DACL, E, F, and G as they actually felt and in trial 2 they were instructed to either "fake good," "fake bad," or "fake average." The order of "actual" and "faked" trials was reversed for conditions 4, 5, and 6. The significant findings for "fake bad" and "fake good" were discussed in terms of the ability of an examiner to detect the manipulative set by means of the grossly deviant scores.

Adult↗
PubMed1982

The excitatory actions of a series of piperidine dicarboxylates on central neurons of the rat, snail, leech and horseshoe crab and on crab neuromuscular junction.

1. Intracellular recordings were made from Helix, Hirudo and Limulus central neurons and from Eupagurus leg muscle and extracellular recordings from rat lateral geniculate neurons. The actions of 2,3-, 2,4-, 2,5- and 2,6-piperidine dicarboxylates were tested on those preparations for both direct effects and interactions with the response to L-glutamate. 2. All four piperidine analogues were devoid of either reproducible direct or indirect effects on Helix and Limulus neurons save that the 2,5-analogue did mimic the action of L-glutamate on Limulus neurons which were inhibited by glutamate. 3. On Hirudo and rat neurons and on Eupagurus muscle, all four piperidines mimicked the action of L-glutamate, all were weak agonists on rat neurones while on Hirudo neurons the 2,5-analogue was the most potent but on Eupagurus muscle, the 2,3- and 2,6-analogues were the most potent. 4. All four piperidines potentiated the action of L-glutamate on rat and Hirudo neurons and on Eupagurus leg muscle and of muscle ejps. 5. The piperidine analogues indicate that there are differences between the glutamate receptors used in the present study and provide some supportive evidence that the preferred conformation for glutamate on crab leg muscle is partially folded while for Hirudo neurons it is more extended.

Animals↗
PubMed1982

The effects of cyclic dicarboxylic acids on spontaneous and amino acid-evoked activity of rat cortical neurones.

1 A series of cyclic dicarboxylic acids were applied by microiontophoresis to neurones in the cerebral cortex of rats anaesthetized with urethane. The object was to examine effects on spontaneous firing rates and any ability to antagonize responses to excitatory amino acids. 2 At relatively low ejecting currents (10-25 nA) cis-2,3-piperidine dicarboxylic acid (cis-2,3-PDA) had no effect on spontaneous firing but selectively antagonized the excitation evoked by n-methyl-D-aspartate (NMDA) without affecting responses to quisqualaife or kainate. At higher ejecting currents (60-100 nA) responses to all three agonists were reduced. 3 Other cis-piperidine dicarboxylic acids and piperazine-2,3-dicarboxylic acid had only weak and variable effects on cell firing and responses to NMDA, quisqualate, kainate, glutamate and aspartate. 4 2, 3-Pyridine dicarboxylic acid (quinolinic acid) produced excitation of all cortical neurones tested. 5 2-Amino-5-phosphono-valeric acid, an NMDA antagonist, reduced responses to quinolinate, implying that this compound can act at NMDA receptors. 6 It is suggested that quinolinic acid may be of physiological interest as a potential endogenous excitant in the nervous system and that cis-2,3-PDA and its N-methyl derivative may be of use in studies of receptor pharmacology and the identification of synaptic transmitters.

Amino Acids↗
PubMed1982

Collagen accumulation in the major structures of the rabbit lung during postnatal development.

In order to study the accumulation of collagen during postnatal development in the major structures of the lung, trachea, bronchi, pulmonary vasculature, and parenchyma were isolated from the lungs of 1-week, 2-month, and 6-month-old rabbits. The concentrations of DNA, protein, and collagen in parenchyma were similar to those for whole lung. DNA per day weight for all structures declined with age. The DNA concentration of trachea at 6 months was only one-tenth that of parenchyma. Protein per dry weight was constant in parenchyma but dropped by half in trachea and nearly that in bronchi. Collagen per dry weight increased significantly between 1 week and 6 months in all structures. The collagen concentrations in vessels, bronchi, and trachea are similar to each other and three to five times that of parenchyma. The total amount of collagen in bronchi, trachea and parenchyma increased approximately 12-, 50-, and 90-fold, respectively, between 1 week and 6 months of age.

Age Factors↗
PubMed1982

Pulmonary fibrosis with small-airway disease: a model in nonhuman primates.

Bleomycin was administered intrabronchially to four baboons in doses of 1 mg/kg for four consecutive weeks. At necropsy 6 months later, the lesions produced differed markedly from those resulting from parenteral administration of bleomycin and consisted of diffuse foci of inflammation and fibrosis of the lung parenchyma associated with small airway lesions. Airway lesions were found in respiratory bronchioles and consisted of bronchiolar wall inflammation, hyperplasia of smooth muscles, and epithelia bronchiolization of adjacent alveolated structures. Many bronchioles were obliterated by the fibrotic process. Biochemical measurements confirmed the histologic appearance of increased lung collagen in three of four animals. These findings indicate that obstruction of small airways by processes which cause lung fibrosis may be separable physiologically from processes which affect only the lung parenchyma.

Airway Obstruction↗
PubMed1982

The effect of theophylline on macrophage elastase secretion.

Theophylline increased the elastolytic activity in conditioned media from murine peritoneal macrophages maintained in a monolayer system. Continuing accumulation of enzyme activity with time required the continuing presence of the drug. Theophylline was active in the presence of a maximally stimulatory concentration of colchicine, a known enhancer of elastase secretion. The effect of theophylline was not due to interference with any elastase inhibitory activity in macrophage conditioned medium. The elastolytic activity from theophylline-stimulated cells exhibited an inhibitor profile similar to the profiles of colchicine-stimulated and unstimulated cells. The results demonstrate that theophylline regulates the amount of extracellular elastolytic activity from murine peritoneal macrophages differently from granulocytic elastase.

Animals↗
PubMed1981

The effect of 2-amino-4-phosphonobutyrate (APB) on acetylcholine release from the rabbit retina: evidence for on-channel input to cholinergic amacrine cells.

The light-evoked release of acetylcholine (ACh) from the rabbit retina was taken as a measure of cholinergic amacrine cell activity. The glutamate analogue DL-(+/-)-2-amino-4-phosphonobutyric acid (APB) prevented the light-evoked release of ACh and also selectively abolished the ON-responses of ganglion cells and the ERG b-wave. It is concluded that the input to cholinergic amacrine cells involves mainly the depolarizing bipolar cells, which subserve ON-channels. L-(+)-stereoisomer of APB was 15 times more potent than the D-(-)-isomer in suppressing ACh release and the b-wave, suggesting that the mechanism of action of APB does not involve antagonism of excitatory amino acids.

2-Amino-5-phosphonovalerate↗
PubMed1981

D-aminophosphonovalerate is 100-fold more powerful than D-alpha-aminoadipate in blocking N-methylaspartate neurotoxicity.

Here we report that the D-isomers of 2-amino-5-phosphonovalerate (D-APV) and alpha-amino-adipate (D-alpha AA) protect arcuate hypothalamic neurons from the potent excitotoxic activity of N-methylaspartate (NMA). Consistent with evidence that APV is much more powerful than alpha AA in antagonizing the neuroexcitatory activity of NMA, we found D-APV nearly 100 times more powerful than D-alpha AA in preventing NMA from destroying arcuate neurons.

2-Amino-5-phosphonovalerate↗
PubMed1981

Phosphonate analogues of carboxylic acids as aminoacid antagonists on rat cortical neurones.

Phosphonate analogues of carboxylic acids have been tested as antagonists of excitatory aminoacids in rat cerebral cortex. (+/-)--2-Amino-7-phosphono-heptanoic acid and the (-)-D-isomer of the pentanoate derivative were more potent and selective antagonists of N-methyl-D-aspartate (NMDA) than compounds tested previously. The results support the view that a distinct population of receptors exists which are preferentially activated by NMDA.

2-Amino-5-phosphonovalerate↗
PubMed1981

The enzymatic digestion of elastin at acidic pH.

The enzymatic degradation of insoluble elastin has been studied at several pH values using purified pepsin and cathepsin D, and neutrophil extracts. Pepsin degraded elastin throughout the pH range of 1.2-4.0 with the optimum pH below 2.0. Molecular sieve chromatography and gel electrophoresis indicated that a spectrum of molecular weight degradation products was produced. The degradation by pepsin was inhibited by sodium dodecyl sulfate (SDS), NaCl and pepstatin. Cathepsin D, which, like pepsin, degrades hemoglobin at acid pH and is inhibited by pepstatin, had no activity against insoluble elastin in the pH range of 3.2-7.2. Extracts of neutrophils degraded elastin above pH 4.0. The pH profile of elastin degradation by neutrophil extracts generally followed that of purified human leukocyte elastase. Our results suggest that during alimentation or pulmonary aspiration of gastric contents, extracellular elastin may be digested by gastric juice at acid pH. Inflammatory cells would not appear to be capable of contributing to such actions until local pH approaches neutrality. Cathepsin D, a major constituent of inflammatory cells, does not digest all types of connective tissue proteins.

Anilides↗