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Biomedical subjects

K M Murphy

Publications and source records attributed to K M Murphy.

At least 145 records · Page 8Linked to original sources
PubMed1984

The permanence of the visual recovery that follows reverse occlusion of monocularly deprived kittens.

While the behavioral and physiologic effects of an early period of monocular deprivation can be extremely severe, they are not necessarily irreversible. Considerable recovery can occur if visual input is restored to the deprived eye sufficiently early, particularly if the nondeprived eye is occluded at the same time (reverse occlusion). This study examines the permanence of the visual recovery promoted by a period of reverse occlusion in kittens that were monocularly deprived from near birth for periods ranging from 3 to 18 weeks. During the period of reverse occlusion, the vision of the initially deprived eye improved from apparent blindness to good levels of acuity. However, upon restoring visual input to the formerly nondeprived eye a surprisingly rapid and reciprocal change occurred in the visual acuity of both eyes. Much of the substantial gain in the vision of the initially deprived eye that occurred during reverse occlusion was lost within 3 weeks, while at the same time the vision of the initially nondeprived eye improved substantially. Nevertheless, in many animals the acuity of the initially nondeprived eye did not recover to levels it had reached prior to reverse occlusion. These results hold important implications for the nature of the mechanisms responsible for the dramatic physiologic effects of monocular occlusion and reverse occlusion on the visual cortex. The results also may help elucidate recent observations on patching therapy in human amblyopia.

Animals↗
PubMed1983

A simple sensitive radioreceptor assay for calcium antagonist drugs.

A radioreceptor assay for calcium channel antagonist drugs described here is based on the ability of these drugs to affect 3H-nitrendipine binding to calcium channels. All the known calcium channel antagonists may be assayed in this manner. The assay can detect 10-100 nM (4 - 40 ng/ml) nimodipine, 10-100 nM (3.5 - 35 ng/ml) nifedipine, 3-30 microM (1.2 - 12 micrograms/ml) prenylamine, 0.1 - 1.0 microM (49 - 490 ng/ml) verapamil and 3-30 microM (1.2 - 12 micrograms/ml) diltiazem. These values cover the range of concentrations of calcium channel antagonists that are clinically important. As the radioreceptor assay detects active metabolites as well as the parent drugs, it should prove a useful adjunct in cardiovascular therapy. The method is more reproducible, simpler and less expensive than other methods such as high pressure liquid chromatography.

Animals↗
PubMed1983

Phorbol ester receptors: autoradiographic identification in the developing rat.

Autoradiography with 3H-labeled phorbol dibutyrate was used for the light microscopic detection of phorbol ester receptors in rat fetuses. In 15- and 18-day fetuses, as well as in adult rats, receptors were found to be concentrated in the central nervous system. The localization of receptors in the ventral marginal zone of the fetal neural tube, the lens of the eye, and other sites suggests a role for phorbol ester receptors in cellular process extension and cell-cell interaction.

Animals↗
PubMed1983

Obligatory role of a Tris/choline allosteric site in guanine nucleotide regulation of [3H]-L-QNB binding to muscarinic acetylcholine receptors.

Tris and choline reduce the maximal binding capacity (RT) of the muscarinic cholinergic antagonist [3H]-L-quinuclidinyl benzilate ([3H]-L-QNB) to atrial membranes, when compared to control values in physiological salt solution (PBS) or NaPi buffer. Addition of guanine nucleotides (GN) to incubations containing choline or Tris reverses the effect of choline and Tris on RT and restores it to levels determined in NaPi or PBS alone. GN addition fails to alter RT or KD values determined in NaPi or PBS in the absence of choline and Tris. This GN effect follows a nucleotide specificity similar to that of the GN regulatory proteins coupled to adenylate cyclase. Tris or choline are required for the expression of GN regulation of [3H]-L-QNB binding to muscarinic acetylcholine receptors (mAChR). An allosteric site recognizing choline and Tris appears involved in the interaction between the guanine nucleotide regulatory protein and antagonist binding to mAChR.

Animals↗
PubMed1983

Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.

Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM. This inhibition involves receptors for the verapamil/prenylamine class of calcium channel antagonists. These diphenylbutylpiperidines also inhibit potassium-induced calcium-dependent contractions of rat vas deferens at concentrations of 40-350 nM. Other phenothiazine and butyrophenone neuroleptics lack such potent calcium-antagonist actions. Diphenylbutylpiperidines also differ from other neuroleptics in their ability to relieve negative symptoms of schizophrenia, such as emotional withdrawal, as well as the positive symptoms which respond to all neuroleptics. We suggest that these unique antischizophrenic actions are related to a blockade by diphenylbutylpiperidines of voltage-operated calcium channels.

Animals↗
PubMed1983

A unitary mechanism of calcium antagonist drug action.

[3H]Nitrendipine binding to drug receptor sites associated with calcium channels is allosterically regulated by a diverse group of calcium channel antagonists. Verapamil, D-600 (methoxyverapamil), tiapamil, lidoflazine, flunarizine, cinnarizine, and prenylamine all reduce [3H]nitrendipine binding affinity. By contrast, diltiazem, a benzothiazepine calcium channel antagonist, enhances [3H]nitrendipine binding. All these drug effects involve a single site allosterically linked to the [3H]nitrendipine binding site. Inhibition of [3H]nitrendipine binding by prenylamine, lidoflazine, or tiapamil is reversed by D-600 and diltiazem, which alone respectively slightly reduce or enhance [3H]nitrendipine binding. Diltiazem reverses the inhibition of [3H]nitrendipine binding by D-600. Our prediction that drugs allosterically regulating [3H]nitrendipine binding should be calcium antagonists is confirmed by calcium antagonism in guinea pig ileum observed with the antihistamine dimethindene, the neuroleptics thioridazine and mesoridazine, and the anticholinergic biperiden.

Binding, Competitive↗
PubMed1983

Adenosine receptor localization in rat testes: biochemical and autoradiographic evidence for association with spermatocytes.

[3H]Cyclohexyladenosine ( [3H]CHA) labels adenosine receptors in rat testes. Testicular adenosine receptors are regulated by guanine nucleotides and divalent cations in a similar fashion to brain adenosine receptors. Endocrine manipulations which selectively decrease sperm cells reduce biochemically determined numbers of [3H]CHA labeled adenosine receptors, whereas adenosine receptor number is not affected by manipulations that primarily influence Leydig cells. Autoradiographic analysis of [3H]CHA binding in the rat testes reveals a localization within seminiferous tubules. Receptor related silver grains occur within tubular epithelium as well as in the lumen of tubules but are absent in interstitial tissue and blood vessels. These data suggest an association of adenosine receptors with spermatocytes within the seminiferous tubule epithelium.

Adenosine↗
PubMed1982

[3H]nitrendipine-labeled calcium channels discriminate inorganic calcium agonists and antagonists.

[3H]Nitrendipine binds with high affinity to brain membranes with a drug specificity indicating association with sites mediating the pharmacologic actions of dihydropyridine slow-calcium-channel antagonist drugs. In brain membranes, [3H]nitrendipine binding is absolutely dependent on the presence of calcium ions. Interactions of cation with [3H]nitrendipine binding sites correlate with their physiologic actions at voltage-dependent calcium channels. Ions such as strontium and barium, which mimic calcium physiologically, share the action of calcium in enhancing [3H]nitrendipine binding. Ions such as lanthanum an cobalt, which block the effects of calcium, can inhibit [3H]nitrendipine binding and block the stimulating actions of calcium. The ability to monitor the influence of ions on an agonist-antagonist continuum at [3H]nitrendipine binding sites provides a molecular probe to explore the regulation of cellular function by calcium and other cations.

Animals↗
PubMedDate not supplied

Development of the visual callosal cell distribution in the rat: mature features are present at birth.

In the present study, the early postnatal distribution and subsequent fate of visual callosal neurons were studied in neonatal rat pups. Previous studies had indicated that the adult pattern of visual callosal neurons was sculpted from an initially uniform distribution in the neonatal cortex. To reexamine this issue, we used a sensitive tracer, latex microspheres conjugated either to rhodamine or fluorescein, that was injected into the occipital cortex of one hemisphere in pups on the day of birth (PND 1), PND 6, or PND 12. Examination of the resulting retrograde labeling of cortical neurons in the opposite hemisphere indicates that features of the mature visual callosal pattern are present as early as PND 1. At all stages of postnatal development, the relative density of callosal projection cells varies consistently across the mediolateral extent of primary visual cortex-it is always highest in the region of the 17/18a border and lowest in the body of area 17. These data strongly suggest that, from the outset, visual cortical neurons in the region of the 17/18a border preferentially make connections with the opposite hemisphere. The results of experiments in which callosal neurons were labeled on the day of birth indicate that only those neurons that have migrated to their final cortical destinations have extended callosal axons into the vicinity of the visual cortex in the opposite hemisphere. The initial pattern of callosal neurons resembles a dense, compact version of the mature one, and the present study suggests that much of the remaining change in the appearance of this pathway may be accounted for by the decrease in the overall density of neurons that is due to expansion of the cortical gray matter during postnatal life. Taken together, these results suggest that the development of the visual callosal pathway in the rat may be more similar to that in the monkey than has been reported previously.

Animals↗
PubMedDate not supplied

Analysis of the postnatal growth of visual cortex.

Development and growth of V1 begins during embryogenesis and continues postnatally. The growth of V1 has direct implications on the organization of features such as the retinotopic map and the pattern of visual cortical columns. We have examined the postnatal growth and two-dimensional shape of V1 in macaque monkeys, cats, and rats. The perimeter, area, and anterior-posterior length of V1 were measured from unfolded and flattened sections from neonatal and adult animals from each of these species. Although there were substantial differences in the overall amount of postnatal growth, from 18% in macaque monkeys to more than 100% in cats, in all three species the shape of V1 did not change during development. Thus, growth of the mammalian visual cortex is well described as an isotropic expansion, so the layout of the global features, such as the arrangement of ocular dominance columns and the retinotopic map, does not need to change during development. Furthermore, quantification of the shape confirms the observations that there is a similar, egg-like oval shape to the visual cortex of these mammalian species.

Animals↗