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Biomedical subjects

M A Zarbin

Publications and source records attributed to M A Zarbin.

At least 55 records · Page 3Linked to original sources

Endogenous adenosine and adenosine receptors localized to ganglion cells of the retina.

Using specific sensitive antisera against adenosine, we have immunocytochemically localized endogenous adenosine to specific layers of rat, guinea pig, monkey, and human retina. Highest adenosine immunoreactivity was observed in ganglion cells and their processes in the optic nerve fiber layer. Substantial staining was also found throughout the inner plexiform layer and in select cells in the inner nuclear layer. Adenosine A1 receptors, labeled with the agonists L-[3H]phenylisopropyladenosine and 125I-labeled hydroxy-phenylisopropyladenosine, were autoradiographically localized. The highest levels of binding sites occurred in the nerve fiber, ganglion cell, and inner plexiform layers of the retina in all the species examined. The distribution of adenosine A1 receptor sites closely parallels that of retinal neurons and fibers containing immunoreactive adenosine. These results suggest a role for endogenous adenosine as a coneurotransmitter in ganglion cells and their fibers in the optic nerve.

Adenosine↗

Autoradiographic localization of high affinity GABA, benzodiazepine, dopaminergic, adrenergic and muscarinic cholinergic receptors in the rat, monkey and human retina.

High affinity gamma-aminobutyric acid, benzodiazepine, strychnine (glycine), dopamine, spirodecanone, alpha 1-adrenergic, alpha 2-adrenergic, beta-adrenergic and muscarinic cholinergic binding sites were localized by semiquantitative autoradiography in rat and, in some instances, in monkey and human retinae using [3H]muscimol, [3H]flunitrazepam, [3H]strychnine, [3H]spiperone, [3H]prazosin, [3H]para-aminoclonidine, [3H]dihydroalprenolol and [3H]quinuclidinyl benzylate, respectively. In nearly every case, the inner plexiform layer (IP) contained a high receptor density. The distribution of alpha 1 sites was unusual in that binding was concentrated in the outer plexiform layer (OP). Dopaminergic and, to a lesser extent, beta-adrenergic binding was diffusely distributed in the outer nuclear layer, the OP, the inner nuclear layer and the IP. The ganglion cell layer displayed significant benzodiazepine binding. The intraretinal distribution of pre- and postsynaptic markers of these neurotransmitters is discussed.

Aged↗

Axonal transport of alpha-bungarotoxin binding sites in rat sciatic nerve.

[125I]alpha-Bungarotoxin (alpha-BuTX) binding sites accumulate both proximal and distal to a ligature positioned around the sciatic nerve of rats. [125I]alpha-BuTX binding sites, localized using quantitative receptor autoradiography, were found to accumulate at nerve ligatures at a relatively constant rate which suggests that they undergo both anterograde and retrograde axonal transport. [125I]alpha-BuTX binding to sections of ligated sciatic nerve was saturable with apparent dissociation constants of 0.97 nM proximal and 0.53 nM distal to the ligature. D-Tubocurarine, nicotine, decamethonium and atropine displaced [125]alpha-BuTX from sciatic nerve sections with affinities comparable to those previously reported for the toxin binding component of rat brain. These data indicate that [125I]alpha-BuTX binding sites pharmacologically similar to those of rat brain are transported in sciatic nerve. Axonally transported toxin binding sites may correspond to those previously localized to the plasma membrane of peripheral nerve axons and on the terminals of motor neurons.

Animals↗

Farber's disease. Light and electron microscopic study of the eye.

A 35-month-old girl had Farber's disease (disseminated lipogranulomatosis) manifested clinically by macular cherry-red spots. The pathologic changes consisted of intracellular inclusions of varying morphologic features and density. The most frequently encountered inclusion was 1.2 micron wide and consisted of flattened stacks of osmophilic lamellae (2.1 to 2.3 nm thick, with 4.4-nm periodicity) oriented in parallel or oblique array ("zebra-body" configuration) and enclosed by a focally discontinuous unit membrane. Some of the inclusions contained curved tubular profiles resembling curvilinear tubular bodies. The retinal ganglion cells were grossly distended with inclusions and showed the greatest pathologic changes.

Adult↗

Autoradiographic localization of (125I-Tyr4)bombesin-binding sites in rat brain.

The binding of (125I-Tyr4)bombesin to rat brain slices was investigated. Radiolabeled (Tyr4)bombesin bound with high affinity (Kd = 4 nM) to a single class of sites (Bmax = 130 fmol/mg of protein); the ratio of specific to nonspecific binding was 6/1. Also, pharmacology studies indicated that the C-terminal of bombesin was important for the high affinity binding activity. Autoradiographic studies indicated that the (125I-Tyr4)bombesin-binding sites were discretely distributed in certain gray but not white matter regions of rat brain. Highest grain densities were present in the olfactory bulb and tubercle, nucleus accumbens, suprachiasmatic and periventricular nuclei of the hypothalamus, central medial thalamic nucleus, medial amygdaloid nucleus, hippocampus, dentate gyrus, subiculum, nucleus of the solitary tract, and substantia gelatinosa. Moderate grain densities were present in the parietal cortex, deep layers of the neocortex, rhinal cortex, caudate putamen, stria terminalis, locus ceruleus, parabrachial nucleus, and facial nucleus. Low grain densities were present in the globus pallidus, lateral thalamus, and midbrain. Negligible grain densities were present in the cerebellum, corpus callosum, and all regions treated with 1 microM unlabeled bombesin. The discrete regional distribution of binding suggests that endogenous bombesin-like peptides may function as important regulatory agents in certain brain loci.

Animals↗

Distribution of muscarinic cholinergic high and low affinity agonist binding sites: a light microscopic autoradiographic study.

The distribution of high vs. low affinity muscarinic agonist binding sites has been determined using quantitative techniques of receptor autoradiography. The low affinity agonist sites predominate in many regions of the forebrain including the cerebral cortex, striatum, hippocampus, amygdala and thalamus. The high affinity agonist sites predominate in the brainstem and represent exclusively the type of muscarinic cholinergic receptor normally present in the principal nucleus of the trigeminal nerve, facial nerve nucleus, hypoglossal nerve nucleus, and in the ventral horn of the spinal cord. The regional localization of these subpopulations provides valuable information for future studies which seek to determine the functional importance of subtypes of muscarinic agonist binding sites.

Animals↗

Amyotrophic lateral sclerosis: alterations in neurotransmitter receptors.

Loss of motor neurons is the primary pathological hallmark of amyotrophic lateral sclerosis. Drug and neurotransmitter receptors are neuronal markers and can be indicators of neuronal connectivity. Knowledge of alterations in receptors in amyotrophic lateral sclerosis should contribute to our understanding of normal spinal cord neurotransmitter systems as well as of the pathophysiology of amyotrophic lateral sclerosis. We therefore used a sensitive, light microscopic in vitro labeling receptor autoradiographic technique to map and quantitate muscarinic cholinergic, glycinergic, and benzodiazepine receptors in three levels of spinal cord from six patients with amyotrophic lateral sclerosis and six age- and sex-matched control patients. In control tissues, the receptor distributions were similar in the three levels of spinal cord and also similar to those found in previous studies with animals. In amyotrophic lateral sclerosis, major reductions in receptor densities were noted in Rexed layer IX, the region containing motor neurons. Reductions were noted in other laminae as well, particularly for muscarinic receptors. The changes in muscarinic receptors were caused solely by changes in high-affinity agonist sites. Reductions in glycine and muscarinic receptors were highly correlated with the degree of motor neuron loss found in the amyotrophic lateral sclerosis patients. The findings in this study point out the usefulness of this receptor mapping technique in understanding the changes in neuronal populations that occur in the degenerative neurological diseases.

Adult↗

Posterior capsule opacification in pseudophakic eyes.

Posterior capsule opacification following extracapsular cataract extraction is a manifestation of proliferation of anterior lens epithelium onto the posterior capsule. In addition to Elschnig pearl formation, vision is decreased in two ways. Multiple layers of proliferated epithelium produce a frank opacity. Also, the lens cells show myofibroblastic differentiation and their contraction produces numerous tiny wrinkles in the posterior capsule resulting in visual distortion. Because the cells that proliferate are anterior lens epithelial cells and because proliferation begins at the site of apposition of anterior capsular flap and the posterior capsule, a wide anterior capsulectomy should help reduce the risk of and delay the onset of visual loss from this complication of extracapsular surgery. Polishing the posterior capsule at the time of surgery will not help in this regard unless there is a complicated cataract with pre-existing posterior migration of lens epithelium. The presence of a potential cleavage plane between the proliferating epithelium and the posterior capsule provides a therapeutic alternative to surgical or laser discission.

Aphakia, Postcataract↗

Axonal transport of beta-adrenergic receptors. Antero- and retrogradely transported receptors differ in agonist affinity and nucleotide sensitivity.

Beta-receptors were measured in longitudinal sections of ligated rat sciatic nerve by autoradiographic localization of 125I-labeled cyanopindolol binding sites. Receptors accumulated at the ligature, both proximally and distally, in a time-dependent fashion. Receptor transport also occurred in an isolated segment of nerve (i.e., a doubly ligated nerve), suggesting that the movement is by fast transport. Pharmacological analysis of the accumulating binding sites indicates that they are beta 2-adrenergic receptors. In competition studies, agonists were 10-30 times more potent on receptors accumulating proximal to the ligature than on distally accumulating receptors, whereas antagonists were equipotent on both. Guanyl-5'-yl-imidodiphosphate (GppNHp) decreased the potency of agonists at proximal receptors in a dose-dependent fashion. Distal receptors were much less sensitive to GppNHp. Other nucleotides displayed varying abilities to mimic the effect of GppNHp, suggesting the involvement of a guanine nucleotide-binding protein in regulating agonist affinity. Thus, presynaptic beta 2-adrenergic receptors were identified in rat sciatic nerve. A small fraction of them apparently moves by fast transport. The anterogradely transported receptors have binding properties which differ from the retrogradely moving receptor and appear to be in functional association with a nucleotide regulatory protein.

Adrenergic beta-Agonists↗

Autoradiographic localization of cholecystokinin receptors in rodent brain.

Cholecystokinin (CCK) receptor binding sites have been localized by autoradiography in the guinea pig and rat central nervous system. [125I]CCK-triacontatriapeptide labeled the sites in brain slices with an observed association constant equal to 0.041 min-1 and a dissociation constant equal to 0.008 min-1. CCK-triacontatriapeptide (CCK-33) and the C-terminal octapeptide of CCK-33 (CCK-8) potently inhibited [125I]CCK-33 binding with Ki's of 2 nM, whereas desulfated CCK-8 (CCK8-ds) and the C-terminal tetrapeptide of CCK-33 (CCK-4) were much weaker. Receptors were concentrated in the olfactory bulb, in the superficial laminae of the primary olfactory cortex, in the deep laminae of the cerebral cortex, and in the pretectal area. Substantial numbers of sites were also found in the basal ganglia, in the amygdala, and in the hippocampal formation. [125I]CCK-33 binding sites appear to be located on fibers of the optic tract and probably on olfactory tract fibers as well. These results are discussed in terms of physiological functions associated with CCK, presynaptic receptors, and axonal flow of CCK receptors.

Animals↗

Distribution of opiate receptors in the monkey brain: an autoradiographic study.

By employing both in vivo and in vitro labeling techniques, opiate receptors were labeled with tritiated diprenorphine in the monkey brain and localized by light microscopic autoradiography. Both methods of labeling gave similar results, allowing a description of discrete areas having opiate binding sites. High concentrations of opiate receptors were found in the substantia gelatinosa of the spinal cord, nucleus tractus solitarius, area postrema, lateral parabrachial nucleus, substantia grisea centralis, several nuclei of the thalamus and hypothalamus, substantia innominata and in the amygdala. In the monkey pituitary, receptors were found in the neurohypophysis. These results correlate well with those found in autoradiographic studies of the rat brain although there are a few notable differences. Many of the opiate receptor distributions can be correlated with anatomical loci of brain functions known to be influenced by administration of opiate compounds.

Animals↗

Axonal transport of muscarinic cholinergic receptors in rat vagus nerve: high and low affinity agonist receptors move in opposite directions and differ in nucleotide sensitivity.

The presence and transport of muscarinic cholinergic binding sites have been detected in the rat vagus nerve. These binding sites accumulate both proximal and distal to ligatures in a time-dependent manner. The results of double ligature and colchicine experiments are compatible with the notion that the anterogradely transported binding sites move by fast transport. Most of the sites accumulating proximal to ligatures bind the agonist carbachol with high affinity, while most of the sites accumulating distally bind carbachol with a low affinity. Also, the receptors transported in the anterograde direction are affected by a guanine nucleotide analogue (GppNHp), while those transported in the retrograde direction are less, or not, affected. The bulk of the sites along the unligated nerve trunk bind carbachol with a low affinity and are less sensitive to GppNHp modulation than the anterogradely transported sites. These results suggest that some receptors in the vagus may undergo axonal transport in association with regulatory proteins and that receptor molecules undergo changes in their binding and regulatory properties during their life cycle. These data also support the notion that the high and low affinity agonist form of the muscarinic receptor represent different modulated forms of a single receptor molecule.

Animals↗

Muscarinic cholinergic receptors flow in the sciatic nerve.

Muscarinic cholinergic receptors build up on the proximal side of a ligature placed on the rat sciatic and vagus nerves. These receptors appear to be flowing down the axons of at least a portion of the nerve fibers present in sciatic and vagus nerves. Most of the anterograde flowing muscarinic binding sites are displaceable with 10(-4) M carbachol indicating that many are high affinity agonist binding sites. These receptors can also be localized in the ganglionic nerve cell bodies in the dorsal root ganglia which contribute fibers to the sciatic nerve. We hypothesize that muscarinic cholinergic receptors are synthesized in the ganglion cell bodies and transported distally in sensory nerve axons in the sciatic nerve.

Animals↗