Oriental hornet venom: effects on cardiovascular dynamics

The hemodynamic effects of the intravenous injection of dry venom of Vespa orientalis were studied in ten dogs. Heart rate, aortic and right ventricular pressure, the first derivative of the right ventricular pressure, the cardiac output and the peripheral vascular resistance were determined. The venom acted within 10 sec and its effects lasted for several minutes. Respiration increased, mean aortic pressure and peripheral vascular resistance fell while cardiac output was increased by 60 per cent. High doses produced arrhythmias, shock and death. Vagotomy and atropine administered prior to the venom administration diminished the respiratory excitation, but had no effect upon cardiac pressures and output. Blockade of 5-hydroxytryptamine, one of the components of the venom, prevented most of the venom action except for vasodilation. Beta-blockade had a lesser effect upon the venom activity. While most of the Oriental hornet venom activity can be explained by the presence of biogenic amines active upon the cardiovascular system, a potent unidentified vasodilator material with possible positive inotropic properties exists in the venom.     

Pharmacological activity of oriental hornet (Vespa orientalis) venom

The pharmacological activity of Oriental hornet (Vespa orientalis) venom has been studied and some of its active substances characterized. The ld₅₀ (i.v.) of venom for albino mice was 2·5 mg per kg.     

Phospholipases B from Japanese yellow hornet (Vespa xanthoptera) venom

Two phospholipases B (Vx I and Vx II) were purified from the venom of the Japanese yellow hornet, Vespa xanthoptera, by sequential chromatography on Sephadex G-100, SP-Sephadex and Mono S columns. They are very similar to each other in molecular and enzymatic properties, though the specific activity of Vx I was one-fifth that of Vx II. They hydrolyze the acyl ester bonds at the 1-position of phosphatidylcholine and lysophosphatidylcholine, therefore, their enzymatic specificities were of the A1 and L1 types.     

Local edema induced by the black-bellied hornet (Vespa basalis) venom and its components

The black-bellied hornet, Vespa basalis, is one of the most dangerous species of wasp in Taiwan. The hornet venom possesses a potent edema-inducing activity in addition to its lethal cardiovascular effect. Rat hind-paw edema induced by the venom was inhibited significantly by antiserotonin compounds (cyproheptadine and methysergide) but not by antihistaminics (chlorpheniramine and diphenhydramine), betamethasone, cromolyn, indomethacin plus nordihydroguaiaretic acid, cellulose sulfate, aprotinin or captopril. However, chlorpheniramine or betamethasone, when given in combination with cyproheptadine, showed a significant further inhibition of the venom-induced edema. Pretreating the rat with compound 48/80 reduced the edematous response to the venom. Four venom components, i.e. the lethal protein, mastoparan B, fraction 3 (containing protease) and fraction 15 (containing serotonin) were involved in the edematous effect of the venom. Paw edema induced by the crude venom and its protein components (lethal protein, mastoparan B and fraction 3) was similar in their responses to antiserotonin compounds and antihistamine (inhibited by cyproheptadine and methysergide but not by chlorpheniramine), while that induced by fraction 15 was inhibited by both. It is postulated that upon hornet stings, fraction 15 is acting as an exogenous serotonin, while the protein components, especially the lethal protein, are responsible for the release of endogenous autacoids in which serotonin plays the most important role in inducing local edema.     

Multiregional cerebral blood flow changes induced by a cholinomimetic drug

The effect of parasympathomimetic drug, carbachol, on regional cerebral blood flow was tested in the rabbit with the 14C-ethanol tissue sampling technique. Intracarotid injection of carbachol significantly increased flow with respect to untreated control animals in 6 out of 10 structures sampled. However, compared with animals to which atropine was also administered, the flow increases were greater with carbachol alone. These effects are discussed in terms of muscarinic and nicotinic activation.     

Phospholipases A and B activities of the oriental hornet (Vespa orientalis) venom and venom apparatus.

Phospholipases A and B activities of the oriental hornet (Vespa orientalis) venom and venom apparatus. Toxicon15, 141–156, 1977.—Oriental hornet venom is a rich source of both phospholipase A (PhA) and phospholipase B (PhB) activities. This was shown by incubating venom with egg yolk or with pure lecithin and lysolecithin. Activity was measured by titrating liberated fatty acids and by phosphorus analyses of separated phospholipids from thin-layer chromatographic plates. Both lecithin and lysolecithin were rapidly hydrolyzed by venom at pH 4 and 8. With egg yolk as substrate, the optimum Ph activity was observed at pH 5 although considerable activity was observed from pH 3·5 to 9·5. In contrast purified substrates showed greater activity at an alkaline pH, whether assay was in the presence of collidine-acetate or Tris buffer or in the presence or absence of ether. Ether dramatically changed the optimal pH for Ph activity, with egg yolk as substrate, from acidic to alkaline. It is not known whether these PhA and PhB activities are dual activities of a single enzyme or activities of two separate enzymes. The venom has neither PhC nor lipase activities.PhA and PhB activities were observed not only in pure venom (V), but also in venom sacs (VS) where the venom is stored, in the acid (venom) glands (H⁺) where the venom is produced, and in the alkaline (Dufours) gland (OH^?) whose function is unknown. The release of free fatty acids from egg yolk at pH 5 was in the ratios of 1 (V): 0·13 (VS): 0·04 (H⁺): 0·30 (OH^?). Measurements of Ph activities in combinations of the above preparations showed that strong activators or inhibitors of the enzyme are not present. The mid-gut, fat body and hemolymph of the hornet showed Ph activity only equal to about one-half of one per cent of that of the OH^? gland.Antisera produced against V, VS, H⁺ and OH^? were cross-reactive and inhibited to varying degrees the Ph activities of each of the above preparations. The highest titre antisera were produced in rabbits injected with V or VS, in contrast to the low titres produced with H⁺ and OH^? glands. Low Ph activity is detectable in the venom sacs 2 days prior to emergence, with 20-fold higher activities being observed at 5 days of age.The oriental hornet may be extremely useful as a rich source of not only PhA but also PhB activities. The effects of this latter enzyme on biological systems have not been thoroughly evaluated. The drastic disruption of phospholipid structure and hydrophobic binding forces between phospholipid and protein, by the combined PhA plus PhB activities, may be responsible for some of the pharmacological actions of hornet venom.     

Depolarization-dependent 45Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine

Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain.     

Dextroamphetamine-induced changes in regional cerebral blood flow

Regional cerebral blood flow (CBF), blood pressure, pulse rate, respiratory rate, end-tidal carbon dioxide and mood states were measured before and after IV injections of 15 mg dextroamphetamine sulfate or saline in 22 physically and mentally healthy normal volunteers. Amphetamine administration was associated with significant increases in systolic blood presure and vigor and decrease in end-tidal carbon dioxide. There were no significant differences between the amphetamine and saline groups on CBF changes. However, there was a non-significant trend towards a post-amphetamine CBF reduction, even after the flow values were corrected for the acute changes in CO₂.     

Effect of obzidan on cerebral blood flow in acute cerebral ischemia

The effect of obsidan on the local cerebral circulation was studied in cats with normal brain circulation and under acute cerebral ischemia. It was demonstrated that obsidan (0.2 mg/kg) increased local cerebral circulation, while on being given in a dose of 1 mg/kg it lowered it in cats with normal brain circulation. In animals with stroke (both on the side with normal circulation and on the side of cerebral ischemia) obsidan (0.2 mg/kg) significantly decreased the local cerebral circulation and destroyed autoregulation of the brain circulation.     

Factors affecting the hemolytic activity of the Oriental hornet (Vespa orientalis) venom and venom sac extracts

Extracts from the venom sacs of the Oriental hornet (V. orientalis) pupae are devoid of either direct or indirect hemolytic activity. However, in venom sac extract obtained during and following eclosion of the imagines, hemolytic activity of both types is present and gradually rises, reaching maximal levels at days 3 or 4. Complete daily evacuation of the venom sac for 5 consecutive days, results in progressive diminution of its hemolytic activity. Soybean trypsin inhibitor and, to a lesser degree, other protease inhibitors, partially suppress the direct hemolytic activity of V. orientalis venom, thus suggesting the possible role of venom proteases as potentiators of the direct hemolytic activity.     

Cholinergic neural regulation of regional cerebral blood flow

Local metabolites have long been considered to play an important physiological role in regulating regional cerebral blood flow (rCBF). However, the evidence reviewed here emphasizes that the regulation of rCBF by central cholinergic nerves is independent of regional metabolism. Activation of the intra cranial cholinergic fibers originating in the nucleus basalis of Meynert (NBM) and septal complex releases acetylcholine in the cortex and hippocampus, which results in vasodilation and an increase in rCBF in the cortex and hippocampus via activation of both muscarinic and nicotinic acetylcholine receptors. Cutaneous sensory stimulation activates the cholinergic nerves originating from the NBM to enhance rCBF. The increase in rCBF at the defuse cortices during walking appears to include an excitation of this NBM-originating cholinergic vasodilation system. Other various inputs to the NBM may have a similar effects to enhance rCBF via activation of that cholinergic system, provided the stimulation is delivered properly. Thus the combination of pharmacological and nonpharmacological techniques may provide a balance in our attempts to improve cholinergic replacement therapy.     

Effects of apomorphine upon local cerebral blood flow

The effects of apomorphine (0.1 mg/kg) upon local cerebral blood flow were examined in anaesthetized baboons. Proportionately similar increases in local cerebral blood flow were observed following apomorphine in the caudate nucleus (40%), cerebral cortex (38%) and cerebellar cortex (26%), despite the marked differences in the density of the dopaminergic innervation to these structures.     

Mechanisms regulating cerebral blood flow as therapeutic targets

Regulation of cerebral blood flow (CBF) is critical for the maintenance of neural function and hence survival of the organism. Since the brain does not store glycogen, unlike muscle, a constant supply of glucose and oxygen are needed for the minute-by-minute demands of cerebral function. This review focuses on important lipid mediators that act as reciprocal regulators of cerebral artery diameter and their potential as targets for therapeutic intervention in diseases such as ischemia, stroke and subarachnoid hemorrhage. Cytochrome P450 metabolism of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) or epoxyeicosatrienoic acids (EETs) provides a mechanism for the constriction and relaxation of cerebral arteries, respectively. Additionally, EETs have mitogenic potential and may contribute to angiogenesis in the brain, which has important implications during recovery from cerebral injury. Finally, we discuss novel inhibitors of 20-HETE formation and actions as well as interventions to enhance EET production in cerebrovascular disease.     

The anti-coagulant properties of an extract from the venom sac of the oriental hornet

An extract from the venom sac of the oriental hornet inhibits the in vitro formation of thromboplastin and thrombin by human plasma and inactivates already formed tissue thromboplastin. The extract has a strong fibrinogenolytic and fibrinolytic activity when tested on purified human fibrinogen, but almost no lytic activity when tested on human plasma. The fibrinolysis is inhibited by soybean trypsin inhibitor as well as by human serum, presumably due to its anti-trypsin activity. Intravenous administration of the sac extract to dogs causes decreased clottability of the whole blood, or the recalcified plasma, and depresses prothrombin consumption and thromboplastin generation. There is a significant decline of the platelet count but a rather mild decrease of fibrinogen. All parameters tend to revert to normal after 2–3 hr. Intraperitoneal envenomation causes severe heparinemia with prolonged clotting, effects which can be reversed by the addition of protamin sulfate. The anticoagulant properties of the venom are abolished by heating at acid or alkaline pH and neutralized by anti-venom immune serum.