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Biomedical subjects

B G Johnson

Publications and source records attributed to B G Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the neonatal rat hippocampus by 2-amino-3-phosphonopropionate.

The effects of excitatory amino acid agonists and alpha-amino-omega-phosphonocarboxylic acid antagonists on phosphoinositide hydrolysis in hippocampal slices of the 7-day neonatal rat were examined. Significant stimulation of [3H]inositol monophosphate formation was observed with ibotenate, quisqualate, L-glutamate, L-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, L-homocysteate, and kainate. N-Methyl-D-aspartate had no effect. Of these agonists, ibotenate and quisqualate were the most potent and efficacious. Stimulations by ibotenate and quisqualate were partially inhibited by L-2-amino-4-phosphonobutyrate (10(-3) M), but this antagonist had no effect on L-glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, or kainate. At 10(-3) M, D,L-2-amino-3-phosphonopropionate completely inhibited ibotenate and quisqualate stimulations, partially inhibited L-glutamate stimulation, and had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-, kainate-, or carbachol-induced [3H]inositol monophosphate formation. Concentration-effect experiments showed D,L-2-amino-3-phosphonopropionate to be five times more potent as an antagonist of ibotenate-stimulated phosphoinositide hydrolysis than L-2-amino-4-phosphonobutyrate. Thus in the neonatal rat hippocampus, like in the adult rat brain, D,L-2-amino-3-phosphonopropionate is a selective and relatively potent inhibitor of excitatory amino acid-stimulated phosphoinositide hydrolysis. Because this glutamate receptor is uniquely sensitive to D,L-2-amino-3-phosphonopropionate, these studies provide further pharmacological evidence for the existence of a novel excitatory amino acid receptor subtype that is coupled to phosphoinositide hydrolysis in brain.

Alanine↗
PubMed1988

Selective inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the rat hippocampus by activation of protein kinase C.

The relative roles of protein kinase C in regulating excitatory amino acid-, cholinoceptor-, and adrenoceptor-stimulated phosphoinositide hydrolysis were studied. Slices of rat hippocampus were prelabeled with [3H]-myo-inositol, and agonist-induced [3H]-phosphoinositide hydrolysis was measured by the formation of [3H]-inositol monophosphate ([3H]-IP) in the presence of lithium ion. Activation of protein kinase C with phorbol 12,13-dibutyrate (PDB) (10(-6) M) completely inhibited ibotenate (IBO) (10(-3) M)-induced [3H]-phosphoinositide hydrolysis. Half-maximal inhibition was observed at about 10(-7) M PDB. Higher concentrations of PDB were required to inhibit stimulation of [3H]-IP by either carbachol (CARB) (10(-3) M) or norepinephrine (NE) (10(-4) M, and only partial inhibition could be attained. Preincubation with staurosporine (STAURO) (10(-5) M) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) (10(-4) M), inhibitors of protein kinase C, potentiated IBO- but not CARB- or NE-induced stimulation of [3H]-IP. PDB inhibition of IBO- or NE-stimulated [3H]-phosphoinositide hydrolysis was reversed by co-addition of STAURO or H-7. In the case of IBO + STAURO, this reversal was to the potentiated level observed with STAURO alone. Enhanced agonist stimulation and reversal of PDB inhibition were also produced by STAURO when [3H]-phosphoinositide hydrolysis was stimulated by either L-glutamate or quisqualate. These experiments show that direct activation of protein kinase C by PDB leads to inhibition of phosphoinositide hydrolysis mediated by excitatory amino acid receptors, cholinoceptors, or adrenoceptors. However, the enhanced agonist-stimulated phosphoinositide hydrolysis elicited by inhibitors of protein kinase C suggests that, when protein kinase C is indirectly activated, only excitatory amino acids rapidly inhibit further receptor-coupling.

Alkaloids↗
PubMed1988

Mediation of serotonin-induced analgesia by the 5HT2 receptor in the pentobarbital anesthetized mouse model.

Serotonin can induce analgesia when injected directly into the brain, but analgesia after peripheral administration has been more difficult to show. The pentobarbital anesthetized mouse (PAM) model, developed to alleviate some of the problems involved in the measurement of tail flick latency, was used to assess the action of peripherally administered serotonin. Mice were anesthetized with about 65 mg/kg of sodium pentobarbital IP and their tail flick latencies measured while they were in stage III anesthesia. In these anesthetized mice, IP serotonin induced a significant analgesia that was much more robust than that found in awake mice. The analgesic effect was dose-dependent from 0.25 mg/kg to 10 mg/kg but was not blocked by the antiopiate naltrexone. Of several psychotropic agents tested, only amitriptyline, mianserin, and trazodone had significant effects on analgesia in the PAM model. The analgesic effect of serotonin was reproduced by the 5HT2 agonist DOI and totally blocked by the 5HT2 antagonist NPP. These results show the utility of the PAM model in studying nonopiate analgesia and suggest that the analgesic action of serotonin is mediated primarily through the 5HT2 receptor.

Analgesics↗
PubMed1988

Excitatory amino acid agonist-antagonist interactions at 2-amino-4-phosphonobutyric acid-sensitive quisqualate receptors coupled to phosphoinositide hydrolysis in slices of rat hippocampus.

Studies were carried out to define the relative affinities and intrinsic activities of excitatory amino acid agonists that activate receptor sites coupled to phosphoinositide hydrolysis in brain. Slices of rat hippocampus were prelabeled with myo-[3H]inositol, and agonist stimulation was indexed by measuring the accumulation of [3H]inositol monophosphate [( 3H]IP) in the presence of Li+. It was observed that ibotenic (IBO) and quisqualic (QUIS) acids both elicit highly significant, concentration-dependent stimulation of phosphoinositide hydrolysis. Whereas maximal stimulation by IBO (10(-3) M) was four- to fivefold over basal values, the maximal effect of QUIS (10(-4) M) was less (about twofold). Based on the relative concentrations required for 50% maximal stimulation, QUIS was 20 times more potent than IBO. Stimulation of phosphoinositide hydrolysis by either IBO or QUIS was additive to the effects of nonexcitatory amino acid agonists (carbachol and norepinephrine) in this tissue. However, the stimulatory effects of IBO plus QUIS were not additive. At greater than or equal to 10(-4) M, QUIS significantly inhibited phosphoinositide hydrolysis by a maximal stimulatory concentration of IBO (10(-3) M) to a level observed with QUIS alone. Other excitatory amino acid agonists, including kainate, N-methyl-D-aspartate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), had no stimulatory effects at concentrations as high as 10(-3) M. The D,L or L forms of 2-amino-4-phosphonobutyric acid (AP4), but not D-AP4, significantly enhanced [3H]IP levels to approximately 135% of basal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1985

Sigma opioid receptor: characterization and co-identity with the phencyclidine receptor.

The properties of the sigma opioid receptor of rat brain cortex have been characterized using the prototypic ligand (+)-[3H] SKF 10,047. Binding to this receptor was rapid, and equilibrium was obtained within 30 min at 37 degrees C. Specific binding was linear with protein concentration up to 500 micrograms/2 ml and was dependent upon protein integrity. Denaturation by boiling destroyed over 95% of the specific binding. A high-affinity binding site with a KD of 150 +/- 40 nM and a maximum binding of 2.91 +/- 0.84 pmol/mg of protein was determined from a Scatchard plot of the binding data. The addition of salt, either NaCl or CaCl2, to the buffers markedly decreased binding, with CaCl2 being more potent than NaCl. A broad pH optimum for specific binding was observed; maximum binding was at pH 9.0. The affinity of a number of ligands for the sigma site and the phencyclidine receptor were compared. The binding (IC50) of 13 ligands to the sigma site showed a correlation of 0.86 (P less than .01) with binding to the phencyclidine site. The data demonstrate that the biochemical properties of the sigma and phencyclidine receptors are similar and support the view that these receptors are one and the same site.

Animals↗
PubMed1985

Thiorphan and analogs: lack of correlation between potency to inhibit "enkephalinase A" in vitro and analgesic potency in vivo.

The potencies of the R and S isomers of thiorphan and rigid analogs of thiorphan to produce analgesia in a mouse hot-plate assay have been compared with their potencies to inhibit enkephalin degradation by rat brain "enkephalinase A." The R and S isomers of thiorphan were equipotent as enzyme inhibitors (IC50 approximately 10(-9) M) but had significantly different analgesic profiles when injected i.c.v. Rigid analogs of thiorphan were less potent enzyme inhibitors (IC50 values of 10(-7) - 10(-4) M) but produced analgesia and potentiated Tyr-D-Ala-Gly-Phe-Met-NH2 induced analgesia at doses (i.c.v.) comparable to thiorphan. These observations suggest that inhibitors of enkephalinase A produce analgesia through a pharmacological mechanism which is not directly related to inhibition of enkephalin degradation.

Amino Acids, Sulfur↗
PubMed1983

Health educational aspects of preventive dental programs for school-age children in 34 countries--final results of an FDI international survey.

The survey was conducted as part of a project of the Working Group on Oral Health Promotion of CORE, in order to provide a basis for the FDI to plan ways to assist its member associations in developing successful preventive dental programs for school-age children. Mail questionnaires were distributed through national dental associations and completed by dental program directors. A total of 119 responses from 34 countries has been analysed. The programs reported tended to be young, supported by public funds, carried out in schools and part of ongoing agency or organizational programs. Instructional activities were the most frequently mentioned service provided routinely for all children, followed by early detection and treatment services. Primary preventive services appeared to be provided least frequently. About 60 per cent of programs served children drinking water from central sources, but only 16 per cent of programs served children drinking optimally fluoridated water. Water fluoridation was the most frequently mentioned procedure that respondents would have liked to see added or extended if additional resources were to be made available. Program organization was the most frequently mentioned reason for program success. The five most frequently mentioned barriers were insufficient financial resources (most often cited), manpower limitations, low public acceptance, non-supportive attitudes among policy makers and inadequate facilities. As a result of the survey three major needs were identified: (1) the need for more efficient application of known effective primary protective methods, especially against dental caries; (2) the need to improve the correspondence between program objectives, the types of services provided and the evaluation methods used to assess and evaluate program achievements; and (3) the need for greater understanding of the scope of community health educational aspects of oral health, prevention and dental treatment. Specification of these and similar problems should lead the FDI working group to recommend priorities on the type of assistance to provide to member nations and the manner of its provision, perhaps in concert with the World Health Organization and the International Association for Dental Research.

Child↗
PubMed1982

Fiber.

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Aged↗