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Biomedical subjects

R D Green

Publications and source records attributed to R D Green.

At least 73 records · Page 4Linked to original sources
PubMed1985

Differences in the properties of muscarinic cholinergic receptors in the developing chick myocardium.

The number of muscarinic cholinergic receptors detected with [3H]quinuclidinyl benzilate (QNB) was constant in embryonic chick heart membranes but increased 2.5-fold by 3 days posthatching; the KD for [3H]QNB did not change. The affinities of the muscarinic receptors for agonists, as determined in in vitro [3H]QNB competition experiments, differed during development. The IC50 values were lowest for 10- to 14-day embryonic heart receptors, intermediate for 18- to 20-day embryonic receptors and highest for 3- to 7-day newborn heart receptors. These apparent differences in agonist affinity were not overcome by guanine nucleotides or monovalent cations alone, but were greatly diminished in the presence of a combination of guanylylimidodiphosphate plus NH4+. Modeling of [3H]QNB/oxotremorine competition curves indicated the presence of three agonist affinity states in membranes from embryonic heart and two in newborn hearts. The KD values for oxotremorine increased during development. The proportion of receptors displaying the highest affinity for oxotremorine was constant at all ages tested whereas the proportion displaying the lowest affinity decreased from 16% in membranes from 12-day embryonic hearts to zero in newborn hearts. The physiological significance of the differences in the properties of the receptors was investigated by assessing their ability to attenuate adenylate cyclase. The efficacy of agonists to attenuate basal adenylate cyclase increased 1.5-fold after birth, whereas the potency of agonists to produce this effect was similar at all ages tested.

Acetylcholine↗
PubMed1985

Additional pressurisation for treating nonresponding cases of serious air decompression sickness.

In this study, 20 years of decompression sickness (DCS) treatment records were reviewed to establish whether or not compression to 50m (165 fsw) was a useful response to serious DCS cases which failed to respond satisfactorily at 18m (60 fsw) breathing oxygen. It was concluded from 14 cases that further compression rarely altered the recovery of cases which were not already recovering at 18m or were of a relatively mild nature. The only case with motor deficits to recover at 50m later relapsed. In general, cases without motor deficits were more likely to be cured, and then only slowly. The only real justification for compression to 50m is rapid deterioration at 18m. This does not guarantee to stop or prevent deterioration as four cases of deterioration at 50m are reported. Nine cases of compression beyond 50m to as deep as 76m (250 fsw) on air are reported with the conclusion that it provides little or no benefit.

Atmospheric Pressure↗
PubMed1984

Improved techniques for the photometric determination of partition coefficients, with particular reference to the chloroform-ammonia solvent system.

Accurate partition coefficients K = Corg/Caq in chloroform-ammonia can be obtained by measuring the absorbance of the aqueous layer, replenishing with fresh aqueous solvent, and remeasuring the absorption after reequilibration. Provided the solute has a reasonably strong UV absorption, only 0.1-5 mg of material is required. Neither the amount, the extinction coefficient, nor (in most cases) the purity of the substrate material need be known. In general, K values ranging from 100 to 0.01 can be measured with a precision of greater than or equal to 10%. A detailed analysis of the absorbance and volumetric error sources permits the optimum combination of experimental conditions such as volume ratios, cell lengths, and absorbance (either direct or differential, or with scale expansion) to be predicted a priori. Quantitative estimates for all primary error sources, such as photometric precision, baseline error, stray light, and volumetric errors were also experimentally determined. The theoretical error model was tested by determining K for aniline under widely ranging experimental conditions and by comparing the experimental standard deviations with those calculated from the theoretical model. The agreement was found to be satisfactory. The method described appears to be of particular usefulness for the determination of extraction or chromatographic parameters of basic drugs.

Ammonia↗
PubMed1984

[3H]5'-N-ethylcarboxamide adenosine binds to both Ra and Ri adenosine receptors in rat striatum.

Adenosine analogs such as 5'-N- ethylcarboxamide adenosine and N6-cyclohexyladenosine stimulate or inhibit adenosine cyclase activity in preparations of rat striatum depending on the assay conditions. N6-cyclohexyladenosine inhibits but does not stimulate adenosine cyclase activity in preparations of hippocampus. These findings suggest that the striatum contains both Ra (stimulatory) and Ri (inhibitory) adenosine receptors while the hippocampus contains only Ri receptors. We have previously shown that [3H]N6-cyclohexyladenosine binds to Ri receptors in rat hippocampus ( Yeung and Green 1983). Comparisons of the characteristics of [3H]5'-N- ethylcarboxamide adenosine and [3H]N6-cyclohexyladenosine binding to hippocampus show that [3H]5'-N- ethylcarboxamide adenosine also binds to Ri receptors with high affinity. [3H]5'-N- ethylcarboxamide adenosine binds to Ri receptors in the striatum and to a second site that is present in striatum but not hippocampus. High affinity binding of both ligands to Ri receptors can be blocked by treatments with N-ethylmaleimide that do not markedly affect [3H]5'-N- ethylcarboxamide adenosine binding to the second site in the striatum. The pharmacological characteristics of the second site indicate that it is the Ra adenosine receptor.

Adenosine↗
PubMed1984

Inhibitory adenosine receptors in the heart: characterization by ligand binding studies and effects on beta-adrenergic receptor stimulated adenylate cyclase and membrane protein phosphorylation.

Adenosine causes negative chronotropic and inotropic effects on cardiac tissue. We have investigated the nature of the cardiac adenosine receptor and its effector mechanisms in preparations of newborn chick heart. The adenosine analog [3H]N6 (L-phenylisopropyl) adenosine (L-PIA), an agonist at R-type adenosine receptors, bound with high affinity to receptors in crude and highly-purified membrane preparations. The KD was 3-5 nM. The receptor density was low in crude membranes (10 fmol/mg protein) but significantly enriched in purified sarcolemma (164 fmol/mg protein). Competition studies showed that N-ethylcarboxamide adenosine and N6(D-phenylisopropyl)adenosine were less potent than N6(L-phenylisopropyl)adenosine at the chick heart adenosine receptor, as expected for an Ri-type adenosine receptor. Gpp(NH)p decreased the binding of [3H]N6(L-phenylisopropyl)adenosine to chick heart membranes, suggesting that the guanine nucleotide converted the receptor to a lower affinity state. N6(L-phenylisopropyl)adenosine inhibited beta-adrenergic receptor stimulated adenylate cyclase activity. The IC50 for cyclase attenuation by N6(L-phenylisopropyl)adenosine was 1 microM. N6(L-phenylisopropyl)adenosine reversed the effect of the beta-receptor agonist isoproterenol on phospholamban phosphorylation in 32P-labelled slices of newborn chick hearts. This effect of N6(L-phenylisopropyl)adenosine was evident by 2 min, had an IC50 of 200 nM, and was prevented by the adenosine receptor antagonist 8-phenyltheophylline. Taken together, the results suggest that the antiadrenergic effects of adenosine on cardiac tissue are mediated by a decrease in membrane protein phosphorylation signalled by activation of Ri-adenosine receptors. The coupling mechanism between receptor activation and protein phosphorylation may be an attenuation of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1984

Nurse practitioners in the medical group setting.

To be at the leading edge in today's rapidly changing world of health care and respond to increasing consumer demands, medical groups must be willing to implement new concepts. The utilization of nurse practitioners is one such concept. Before implementation, however, the idea should be thoroughly reviewed from all standpoints, including role of the practitioner, education and training, scope and areas of practice, legalities, billing, third-party reimbursement, record documentation, income distribution, and control of practice. Nurse practitioners in the medical group setting can be helpful in increasing patient satisfaction and improving quality of care.

Group Practice↗
PubMed1984

Reciprocal modulation of agonist and antagonist binding to inhibitory adenosine receptors by 5'-guanylylimidodiphosphate and monovalent cations.

Previous work from this laboratory showed that rat hippocampal membranes contain adenosine receptors that mediate GTP-dependent inhibition of adenylate cyclase activity (Yeung, S. -M. H., and R. D. Green (1983) J. Biol. Chem. 258: 2334-2339). Furthermore, we reported that guanine nucleotides decrease agonist and increase antagonist binding to these adenosine receptors. The present study examines the effects of monovalent cations and guanine nucleotides, alone and in combination, on the binding of agonist [( 3H]N6(L-phenylisopropyl)adenosine) and antagonist [( 3H]diethylphenylxanthine) radioligands to adenosine receptors in rat hippocampal membranes. Low concentrations of monovalent cations (less than or equal to 100 mM) did not affect agonist binding. 5'-Guanylylimidodiphosphate (Gpp(NH)p) alone increased the KD of the agonist without affecting the maximal number of sites labeled by the agonist (Bmax); in the presence of monovalent cations, Gpp(NH)p both increased the KD and decreased the number of sites labeled by the agonist. In contradistinction, Gpp(NH)p increased the maximal number of sites to which the antagonist bound without affecting its KD, while monovalent cations decreased the KD of the antagonist both in the absence and the presence of Gpp(NH)p. It is proposed that both agonist and antagonist-receptor complexes exist in three distinct affinity states and that the transitions between these states are modulated by guanine nucleotides and monovalent cations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1984

Adenosine analogs and sleep in rats.

The effects of N6-L-(phenylisopropyl)adenosine, cyclohexyladenosine and adenosine-5'-N-ethylcarboxamide on sleep were examined in rats. These effects consist of 1) increased slow-wave sleep2 from 6.6 to 45.7%, in all doses used for cyclohexyladenosine and adenosine-5'-N-ethylcarboxamide and for 0.1 and 0.3 mumol/kg of N6-L-(phenylisopropyl)adenosine and 2) increased values for rapid-eye-movement-sleep, amounting to 56.2 and 51.6% for 0.1 mumol/kg of cyclohexyl-adenosine and 0.3 mumol/kg of N6-L-(phenylisopropyl)adenosine, respectively. Slow-wave sleep1 decreased but values for wakefulness and total sleep were unchanged for 0.03, 0.1 and 0.3-mumol/kg doses of the drugs. Only 0.9-mumol/kg dose of cyclohexyladenosine and N6-L-(phenylisopropyl)adenosine increased wakefulness and decreased total sleep, whereas the same dose of adenosine-5'-N-ethylcarboxamide increased total sleep during the 0- to 3-hr time interval. All three agents reduced rapid-eye-movement sleep at the 0.9-mumol/kg dose. The results indicate that the effect on sleep of all three adenosine analogs was obtained with nanomolar doses of the drugs and that it diminished or disappeared when the drug dose reached micromolar range (0.9 mumol/kg). It appears, therefore, that activation of A1 rather than A2 receptors contributed to the sleep effects of the drugs because adenosine and adenosine analogs activate A1 receptors in nanomolar quantities whereas activation of A2 receptors requires micromolar concentration of these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1983

Hypnotic effects of deoxycorformycin in rats.

Rats implanted with EEG and EMG electrodes were treated with deoxycoformycin (0.5 or 2.0 mg/kg, i.p.), and polygraphically recorded for 6 h. Deoxycoformycin is a potent inhibitor of adenosine deaminase and would be expected to elevate the levels of adenosine in the central nervous system. The 0.5 mg/kg dose of the drug increased REM sleep and reduced REM sleep latency while the dose of 2.0 mg/kg increased deep slow-wave sleep (S2). These results appear to be consistent with those reported previously for the adenosine analog, N6-(L-phenylisopropyl)-adenosine (L-PIA) and indicate a hypnotic role for adenosine.

Adenosine Deaminase Inhibitors↗
PubMed1983

The effects of adenosine and 2'-deoxycoformycin on sleep and wakefulness in rats.

The effects of adenosine (12.5 nmol/rat, i.c.v.) and 2'-deoxycoformycin (2.0 mumol/kg, i.p.) on sleep and wakefulness were examined in rats. Adenosine significantly decreased wakefulness and increased both deep slow-wave sleep and total sleep. 2'-Deoxycoformycin, a potent inhibitor of adenosine deaminase, was administered at a dose which did not produce significant sedative and hypnotic effects, when given alone (although a 4-fold greater dose of this drug has been shown to be hypnogenic in rats) in order to examine the possible potentiation of exogenously administered adenosine. No such potentiation was observed, since treatment with both drugs produced effects qualitatively similar, although not statistically significant, to those of adenosine alone. These data clearly indicate that adenosine is a hypnogenic substance in rats and suggest that these effects may involve adenosinergic receptor-mediated modulation of the activity of central adenylate cyclase.

Adenosine↗
PubMed1982

Modulation of striatal dopaminergic function by local injection of 5'-N-ethylcarboxamide adenosine.

Rats rotated to the left when 5'-N-ethylcarboxamide adenosine (NECA) was injected into the left caudate nucleus and apomorphine was administered subcutaneously. The combination of NECA and apomorphine was more potent than L-(phenylisopropyl)adenosine and apomorphine in eliciting rotation, suggesting the involvement of adenosine receptors of the Ra type. The response was reduced when 2',5'-dideoxyadenosine was injected along with NECA into the caudate nucleus or when theorphylline was given intraperitoneally. Higher doses of apomorphine elicited a self-mutilatory response after the injection of NECA into the caudate nucleus. These results suggest that adenosine may be involved in the modulation of dopaminergic function in the striatum.

Adenosine↗
PubMed1980

Adenosine transport by a variant of C1300 murine neuroblastoma cells deficient in adenosine kinase.

The uptake of adenosine by an adenosine kinase deficient variant of C1300 murine neuroblastoma cells has been studied in the absence and in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine, a potent adenine deaminase inhibitor. Although 100 micro M inhibitor completely blocks the metabolism of adenosine under the conditions studied, the uptake of adenosine is concentrative, i.e., the intracellular adenosine concentration exceeds the extracellular concentration. This concentrative effect decreases as the concentration of adenosine increases and is hypothesized to be due to the binding of adenosine to an intracellular component. Despite this concentrative effect, we believe that the kinetics of uptake, as determined in experiments with short (10-20 s) uptake periods, reflect the kinetics of adenosine transport by a facilitated diffusion process. This nucleoside transport system appears to be nonspecific in that the transport of adenosine is competitively antagonized by thymidine. It does not appear to be necessary to inhibit adenosine deaminase in order to study transport in these cells as the Km for transport is not affected by the presence of erythro-9-(2-hydroxy-3-nonyl)adenine. However, erythro-9-(2-hydroxy-3-nonyl)adenine does depress the V for transport. This effect of the inhibitor is probably not due to the inhibition of adenosine deaminase as the transport of thymidine is similarly affected.

Adenine↗