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Z Wollberg

Publications and source records attributed to Z Wollberg.

At least 37 records · Page 2Linked to original sources

Evolution of the sarafotoxin/endothelin superfamily of proteins.

Sixteen protein and nucleic acid sequences from the vasoconstrictor sarafotoxin/endothelin/endothelin-like superfamily of peptides were studied, and the evolutionary relationships between the sarafotoxin and endothelin gene families as well as the phylogenetic topology within each gene family and the three endothelin subfamilies was reconstructed. The endothelin gene family has diverged from an ancestral gene that has experienced an exon duplication event followed by two gene duplication events. The sarafotoxins' lineage diverged from the ancestral gene prior to the first endothelin gene duplication event. Analysis of the resulting phylogenetic trees revealed that in several lineages, the peptides have independently accumulated identical replacements in position 2, therefore supporting the hypothesis that residue 2 is crucial to their activity.

Amino Acid Sequence↗

Invasion of visual cortex by the auditory system in the naturally blind mole rat.

Previously we have shown that the dorsal lateral geniculate body (LGB), which is strictly visual in sighted mammals, receives a strong auditory input in the naturally blind mole rat (Spalax ehrenbergi). Here we show with the 2-deoxyglucose technique and with single-unit recordings that in this species the initially non-degenerated visual cortex, as defined by its connection with LGB, is also activated by the auditory modality. These findings suggest that cross-modal compensation may occur as a natural consequence of the degeneration of a sense organ.

Animals↗

The evolutionary history of the sarafotoxin/endothelin/endothelin-like superfamily.

The evolutionary relationships among 17 protein and nucleic acid sequences from the sarafotoxin/endothelin/endothelin-like superfamily of peptides were studied. The endothelin/endothelin-like gene family has diverged from an ancestral gene that has experienced an exon duplication event followed by two complete gene duplications. The sarafotoxin lineage diverged from the ancestral gene prior to the first gene duplication event. In several lineages, the peptides have independently accumulated identical amino acid replacements in position 2. This finding supports the hypothesis that residue 2 is crucial to biological activity.

Amino Acid Sequence↗

Auditory cortex of the long-eared hedgehog (Hemiechinus auritus). I. Boundaries and frequency representation.

The boundaries of the primary auditory cortex of the long-eared hedgehog, Hemiechinus auritus, were determined by single-cell recordings, myeloarchitecture and retrograde horseradish peroxidase labeling in the medial geniculate, using anesthetized animals. The auditory cortex is located on the lateral surface of the temporal cortex, medial to the rhinal fissure. Responses to pure tones revealed an orderly representation of best frequencies in the primary auditory cortex, with low frequencies represented rostrally and high frequencies caudally. A second auditory field caudal to the primary one was indicated.

Animals↗

SRTX-d, a new native peptide of the endothelin/sarafotoxin family.

The primary structure of a new sarafotoxin, SRTX-d, from the venom of Atractaspis engaddensis is described. SRTX-d differs from SRTX-b in two substitutions: Ile19 instead of Val and Thr2 instead of Ser. The toxicity of SRTX-d and its vasoconstriction potency are very low in comparison to SRTX-a and SRTX-b, whereas its IC50 for 125I-SRTX-b binding is similar to that of SRTX-b. It is suggested that the Thr to Ser substitution, which is shared by two additional weak members of the endothelin/sarafotoxin family, SRTX-c and ET-3, affects the biological activity of SRTX-d as well.

Amino Acid Sequence↗

Functional endothelin/sarafotoxin receptors in the rat uterus.

Functional receptors for the peptides of the endothelin (ET) and sarafotoxin (SRTX) families were detected in the rat uterus. These receptors specifically bind 125I-SRTX-b (Bmax = 220 fmol/mg protein), as well as ET-1, ET-3 and SRTX-c (IC50's 10, 5, 300 and 780 nM, respectively). Activation of the uterine ET/SRTX receptors induced dose-dependent phosphoinositide (PI) hydrolysis and three typical contractile responses: 1) increase in the muscle tonic tension; 2) increase in frequency of the spontaneous rhythmic contractions; 3) decrease of relaxation in each spontaneous rhythmic cycle. All three effects appeared at doses as low as 0.5-1 nM. Dose responses yield ED50 values of 5.5, 30 and 680 nM for ET-1, SRTX-b and ET-3, respectively. SRTX-c was the least effective peptide in achieving decrease in relaxation. In view of these results, and since the uterine responses to the peptides were almost immediate and reversible, we suggest that the functional ET/SRTX receptor of the rat uterus that is coupled to PI hydrolysis may be of physiological significance.

Animals↗

Vasoconstrictor effects of sarafotoxins in rabbit aorta: structure-function relationships.

The sarafotoxins SRTX-a, b and c from the venom of the snake Atractaspis engaddensis are 21-amino acid peptides that affect the cardiovascular system. They are strong vasoconstrictors, the potency of which may be in correlation with their primary structure: SRTX-a, which differs from SRTX-b in a single amino acid residue (Asn instead of Tyr), shows about half of its maximal vasoconstriction, while SRTX-c, which differs in 3 additional residues is a very weak vasoconstrictor and, at high doses, shows vasodilatory effects. Sequential application of the three isotoxins result in a summated response.

Amino Acid Sequence↗

Auditory pathway and auditory activation of primary visual targets in the blind mole rat (Spalax ehrenbergi): I. 2-deoxyglucose study of subcortical centers.

The blind mole rat Spalax ehrenbergi is a subterranean rodent that shows striking behavioral, structural, and physiological adaptations to fossorial life including highly degenerated eyes and optic nerves and a behavioral audiogram that indicates high specialization for low-frequency hearing. A 2-deoxyglucose functional mapping of acoustically activated structures, in conjunction with Nissl/Klüver-Barrera-stained material, revealed a typical mammalian auditory pathway with some indications for specialized low-frequency hearing such as a poorly differentiated lateral nucleus and a well-developed medial nucleus in the superior olive complex. The most striking finding was a marked 2-deoxyglucose labeling of the dorsal lateral geniculate body and of cortical regions that correspond to visual areas in sighted rodents. The results render the blind mole rat a good model system for studying natural neural plasticity and intermodal compensation. In this report, we confine ourselves to the subcortical levels. The cortical level will be dealt comprehensively in a following paper.

Acoustic Stimulation↗

Sarafotoxin receptors mediate phosphoinositide hydrolysis in various rat brain regions.

Sarafotoxin-b, a potent snake vasoconstrictor peptide homologous to the mammalian endothelial vasoconstrictor endothelin, induces phosphoinositide (PI) hydrolysis in various brain regions of the rat. Sarafotoxin-b induced PI hydrolysis is largely independent of extracellular Ca2+ and is detected in all brain regions where toxin-binding sites are found. These results point to the existence of a hitherto undetected neuroreceptor associated with the PI cycle.

Animals↗

Tuning properties of auditory cortex cells in the awake squirrel monkey.

Pure tone bursts elicited in primary auditory cortex (AI) cells of the awake squirrel monkey a wide range of response patterns which consisted of one or more excitatory or inhibitory temporal response components. In almost 60% of these cells, response patterns were frequency and/or intensity dependent. Response components such as early and late onset excitation, offset excitation and on-off excitation; as well as tonic excitation or inhibition often varied independently with changes in these stimulus parameters. Individual cells were therefore considered as multiple bandpass filters, and each discrete response component was analyzed separately for its tuning properties. A correlation between best frequencies of the various excitatory components (BEF), and between BEFs and best frequencies of inhibitory components (BIF), in cells which responded with more than one discrete response component, disclosed a significantly higher correlation between BEF/BIF pairs compared with BEF/BEF pairs, presumably reflecting certain "lateral inhibition like" processes. Applying Q10dB factor, and square root of Hf-square root of Lf bandwidth at 10 dB above threshold, as measures of the "sharpness" of response areas, revealed that approximately 65% of all response areas could be defined as "narrow" by either one of these 2 measures, with no distinction, in that regard, between excitatory and inhibitory components. The average response bandwidths of the narrowly and the broadly tuned components, at 10 dB above threshold, were 0.4 +/- 0.18 and 1.42 +/- 0.68 octaves respectively. A comparison with the medial geniculate body (MGB) of the squirrel monkey, applying the square root of Hf-square root of Lf measure of sharpness of tuning, showed a significantly higher proportion of narrow response areas in the AI. "Narrow" response areas in both these regions were equally narrow, whereas the "broad" response areas of MGB cells were significantly broader. These results suggest a sharpening of response areas throughout the geniculo-cortical transformation.

Animals↗

Prediction of linear and non-linear responses of MGB neurons by system identification methods.

In sensory physiology, various System Identification methods are implemented to formalize stimulus-response relationships. We applied the Volterra approach for characterizing input-output relationships of cells in the medial geniculate body (MGB) of an awake squirrel monkey. Intraspecific communication calls comprised the inputs and the corresponding cellular evoked responses--the outputs. A set of vocalization was used to calculate the kernels of the transformation, and these kernels subserved to predict the responses of the cell to a different set of vocalizations. It was found that it is possible to predict the response (PSTH) of MGB cells to natural vocalizations, based on envelopes of the spectral components of the vocalization. Some of the responses could be predicted by assuming a linear transformation function, whereas other responses could be predicted by non-linear (second order) kernels. These two modes of transformation, which are also reflected by a distinct spatial distribution of the linear vis-à-vis non-linear responding cells, apparently represent a new revelation of parallel processing of auditory information.

Acoustic Stimulation↗

Are seismic communication signals transmitted by bone conduction in the blind mole rat?

The anatomy of the middle ear of the blind mole rat, a subterranean rodent that uses seismic signals for long distance communication, is described qualitatively and quantitatively. The ossicular chain is of the parallel type with a lever arms ratio of 0.55 and an effective areal ratio of stapedial footplate to eardrum of 0.09. Assuming an ideal mechanical transform, the calculated fraction of acoustical energy theoretically transmitted to the cochlea, indicate low efficiency for airborne sounds. This is in accordance with the relatively high electrophysiological and behavioral threshold, shown previously. We suggest that a unique morphology of the middle ear and of the articulation between the lower jaw and the skull, as well as a peculiar 'jaw listening behavior' enable seismic vibrations to be transmitted to the inner ear mainly by bone conduction, thereby compensating for the limitation in receiving airborne signals.

Animals↗

Characterization and localization of a novel neuroreceptor for the peptide sarafotoxin.

We have recently shown that the rat atrium and brain contain specific high affinity receptors for the novel snake vasoconstrictor peptide sarafotoxin-b (SRTXb), and demonstrated toxin-induced phosphoinositide hydrolysis. Here we report on the characteristics of 125I-SRTXb receptors and their regional distribution in rat brain. 125I-SRTX receptors in the rat brain bind the toxin rapidly and with high affinity. The binding was not inhibited by ligands of known neurotransmitter receptor and ion channels. 125I-SRTX receptors have a distinctive regional distribution. The highest densities were observed in the cerebellum, thalamus and hypothalamus (850, 550 and 450 fmol/mg protein, respectively) and the lowest densities in the caudate and cerebral cortex (82 and 62 fmol/mg protein, respectively). Taken together our results suggest that mammalian brains contain a hitherto undetected neuroreceptor that may operate in neurotransmission with a "SRTX-like" brain peptide, similar to the SRTX homologous vasoconstrictor peptide of the mammalian endothelium endothelin.

Animals↗

Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain.

Sarafotoxins, a group of 21-residue cardiotoxic peptides from snake venom that induce coronary vasoconstriction, show high-affinity binding to rat atrial and brain membranes and activate the hydrolysis of phosphoinositides. Neither their binding nor their activity is affected by blockers or activators of known receptors and ion channels, suggesting that sarafotoxins act either directly on the phosphoinositide phosphodiesterase system or on a novel receptor. Their amino acid sequence shows a high degree of homology with that of endothelin, a recently described 21-residue vasoconstrictor peptide found in porcine aortic endothelium. This is remarkable, since endothelin is a natural compound of the mammalian vascular system while sarafotoxins are highly toxic components of snake venom.

Amino Acid Sequence↗

A novel cardiotoxic polypeptide from the venom of Atractaspis engaddensis (burrowing asp): cardiac effects in mice and isolated rat and human heart preparations.

A new cardiotoxic polypeptide isolated from the venom of the snake Atractaspis engaddensis has an LD50 of 15 micrograms/kg body weight in white mice. Intravenous administration in mice of lethal doses of the toxin causes, within seconds, marked changes in the ECG, consisting primarily of a transient slope elevation of the S-T segment, a temporary diminution of the S-wave and an increase in the amplitudes of the R- and T-waves. Concomitantly, and apparently unrelated to these changes, a severe A-V block develops and leads to complete cardiac arrest within a few min. Studies with rat and human isolated heart preparations showed that the toxin exerts a powerful coronary vasoconstriction (rats), and positive inotropic effects (rats and humans).

Animals↗

Identification of MGB cells by volterra kernels. III. A glance into the black box.

Neuronal systems can be described by their transfer functions, which can be represented by a Volterra series expansion. While the high level of abstraction which characterizes this representation enables a global description, it is problematic, to some extent, in the context of linking the formal representation of the system to its actual structure. The formal representation is unique, yet there are multiple physical realizations of this representation. Separating the system's output into its logical components (linear, cross-linear, and self nonlinear, in this study), and inspecting the relative contribution of these components, might provide a key towards a linkage between the formal and actual representations. Based on results drawn from identification of MGB cells of the squirrel monkey, it is shown that the relative contributions can be described in neurobiological terms such as excitation and inhibition and thus be attributed to actual subsystems.

Animals↗