PubMed Health⌕ Search

Biomedical subjects

E Kochva

Publications and source records attributed to E Kochva.

At least 37 records · Page 2Linked to original sources
PubMed1991

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↗
PubMed1990

Unusual aspects of the venom apparatus of the blue coral snake, Maticora bivirgata.

Light and transmission electron microscopic observations of the venom gland of the blue coral snake revealed a main venom gland and a long duct. The main secretory cell showed characteristic features of a protein secreting cell, with small microvilli, and a cytoplasm containing vacuoles and vesicles. Another type of "dark cell" and a third type of "basal cell" were also seen. "Nerve terminals" supplying the gland showed pleomorphic vesicles. The compressor muscle surrounding the venom gland showed the A band, Z disc, and H zone. Satellite cells were seen among muscle fibres. The neuromuscular junctions supplying the muscle showed clear vesicles. Scanning electron microscopy of the fangs showed the entrance lumen, discharge orifice, suture and the dental ridge. These findings are compared with relevant structures in other snake species.

Animals↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Snake acetylcholine receptor: cloning of the domain containing the four extracellular cysteines of the alpha subunit.

The acetylcholine receptor (AcChoR) at the neuromuscular junction of elapid snakes binds cholinergic ligands but unlike other muscle AcChoRs does not bind alpha-bungarotoxin. Numerous studies indicate that the ligand-binding site of the AcChoR includes cysteine residues at positions 192 and 193 of the alpha subunit. We have previously shown that a synthetic dodecapeptide corresponding to residues 185-196 of the Torpedo AcChoR alpha subunit contains the essential elements of the ligand-binding site. In an attempt to elucidate the structural basis for the precise binding properties of snake AcChoR, we sequenced a portion of the snake AcChoR alpha subunit. First, a mouse AcChoR alpha-subunit cDNA probe was used to screen a size-selected snake (Natrix tessellata) genomic library. A genomic clone was isolated and was found to contain sequences homologous to the exon including the first two cysteines (Cys-128 and -142) of AcChoR alpha subunit. The domain of the alpha subunit from Natrix and cobra AcChoR (amino acid residues 119-222), which contains the four extracellular cysteines (128, 142, 192, and 193), was amplified by reverse transcription of mRNA and the polymerase chain reaction and then sequenced. The deduced amino acid sequence showed that the snake alpha subunit contains the two tandem cysteines at positions 192 and 193, resembling all other AcChoR alpha subunits. Sequence comparison revealed that the cloned region of the snake alpha subunit is highly homologous (75-80%) to other muscle AcChoRs and not to neuronal AcChoR, which also does not bind alpha-bungarotoxin. In the presumed ligand-binding site, in the vicinity of Cys-192 and Cys-193, four major substitutions occur in the snake sequence--at positions 184 (Trp----Phe), 185 (Lys----Trp), 187 (Trp----Ser), and 194 (Pro----Leu). In addition, Asn-189 is a putative N-glycosylation site, present only in the snake. These changes, or part of them, may explain the lack of alpha-bungarotoxin-binding to snake AcChoR.

Amino Acid Sequence↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

Species specific sensitivity towards the hemorrhagin of Ophiophagus hannah (Elapidae).

The filtration pattern of Ophiophagus hannah venom on Sephadex G-75 shows several peaks. The first peak, S1, includes high molecular weight proteins and contains the hemorrhagic and proteolytic activities. The proteolytic fractions overlap the hemorrhagic fractions, but are not identical with them. The crude venom and the high molecular weight peak have caseinase, benzoyl-L-arginine ethyl ester hydrolase and kallikrein-like activities, but not collagenase, gelatinase, thrombin, plasmin or urokinase-like activities. The hemorrhagin of Ophiophagus hannah shows species specific differences in its hemorrhagic effects: it causes hemorrhages in rabbits and hares (Lagomorpha), but not in rats, mice or guinea-pigs (Rodentia).

Animals↗
PubMed1986

Gel permeation patterns of venoms from eleven species of the genus Vipera.

Gel filtration of venoms from eleven species of the genus Vipera shows similar patterns on Sephadex G-75, with three groups of protein peaks. The second group, which contains phospholipase A2, is variable among the species. As found in some other viperids, the venom of V. bornmuelleri shows synergism between phospholipase A and other fractions that considerably increases lethal potency.

Animals↗
PubMed1986

Coronary vasospasm as the primary cause of death due to the venom of the burrowing asp, Atractaspis engaddensis.

The venom from the snake Atractaspis engaddensis has been shown to be cardiotoxic in anesthetized mice. The effects of the venom were further tested on both atrial and Langendorff heart preparations of rats, in addition to its cardiovascular effects in anesthetized mice. The venom (0.1 mg/kg, i.v.) produced a transient hypertension followed by fluctuation of arterial blood pressure, leading to cardiac failure within 20 min. Various kinds of ECG changes, including S-T depression and A-V block were observed within 10 sec after injection. A dose as low as 1 microgram of venom injected into the perfusion system produced a marked coronary vasospasm in the Langendorff heart preparation, whereas no deleterious effect was found in the atrial preparation at a concentration as high as 10 micrograms/ml. It is concluded that the cardiotoxic effects of the venom are primarily due to coronary vasospasm.

Animals↗
PubMed1986

Isolation and characterization of a proteolytic factor from the venom of Vipera palaestinae.

A proteolytic enzyme which is active on collagen and gelatin was isolated from the venom of Vipera palaestinae. The enzyme showed an optimal temperature of 45 degrees C and an optimal pH of 8.0. It was inhibited by snake blood serum, but not by EDTA or trypsin inhibitors. The enzyme was completely separated from one of the venom hemorrhagins, which accompanied it through the purification procedure. The possible evolution of hemorrhagins from proteolytic enzymes is discussed.

Achilles Tendon↗
PubMed1985

Lethal factors and enzymes in the secretion from Duvernoy's gland of three colubrid snakes.

Secretion from Duvernoy's gland of the colubrid snakes Malpolon, Spalerosophis, and Thamnophis was obtained by pilocarpine stimulation and tested for lethality and selected enzymatic activities. Pools of secretion from Malpolon and Spalerosophis were fractionated by gel filtration, and several major active fractions were examined. The secretion from Malpolon had an LD50 of 6.5 micrograms/gm in mice; two lethal fractions with LD50's of 2.75 micrograms/gm and 4.5 micrograms/gm were isolated. One of these fractions appears to be a basic phospholipase A with a molecular weight of about 17,000. Spalerosophis had a secretion with an LD50 of 2.75 micrograms/gm in mice; one main lethal fraction with an LD50 of 2.5 micrograms/gm was isolated. Secretion from Thamnophis had an LD50 of 33.3 micrograms/gm; it was not fractionated owing to a paucity of material. At least two of the snake species examined have toxic secretions that may be important during feeding by killing or weakening and helping to subdue the struggling prey.

Animals↗