Proteinase Inhibitors: An Overview of their Structure and Possible Function in the Acute Phase
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
A kunin domain, exemplified by aprotinin, is composed of 58 amino acid residues (Figure 1). Since we now recognize over 30 vertebrate kunins, the degree of protein sequence identity between them is rather low and members of the family are recognized mainly by the position of six cysteine residues that comprise the three disulfide bridges of aprotinin (Figure 2). The inhibitory activity of aprotinin is dependent on a compact structure that relies on the correct formation of the three disulfide bonds,25 and it is probable that other kunins have the same requirement. Based on sequence identity relationships, we recognize some kunins that are not thought to be proteinase inhibitors, the most well known being the β-bungarotoxin B-subunits. Presumably, inhibitory activity has been lost as a result of deletion of the P1 residue.26 Mammalian kunins are often embedded in other proteins, which often undergo complex posttranslational processing events. We currently recognize the mammalian kunins listed in Figure 3. At the moment, there are no definite roles assigned to these inhibitors, although it is possible that two of them, trypstatin and LACI, may be involved in regulating blood coagulation.
Neurotransmission at Parasympathetic Nerve Endings
Kenneth J. Broadley in Autonomic Pharmacology, 2017
The venom of the black widow spider (Latrodectus mactans tredecimguttatus) (BWSV) and the β-bungarotoxin component of the venom from the Taiwan banded krait (see nicotinic binding of the α-bungarotoxin) also exert powerful effects on Ach release from cholinergic nerves. They initially cause clumping of vesicles at the neuronal membrane, many showing fusion with the membrane. Miniature postjunctional excitatory potentials occur. Subsequently, these potentials cease, and vesicles become permanently fused with the axonal membrane which becomes expanded and convoluted. At this point synaptic transmission is blocked. BWSV has a similar action on noradrenaline release from sympathetic nerve terminals.
Striated MusclesSkeletal and Cardiac Muscles
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
MEPPs are abolished by curare and increased in frequency and amplitude by acetylcholinesterase inhibitors. MEPP frequency is directly related to extracellular calcium concentration and inversely so to magnesium. Theophylline, catecholamines and cardiac glycosides increase MEPP frequency. The venoms of the black widow (α-latrotoxin) and the Australian redback spiders increase MEPP frequency greatly by enhancing vesicle discharge and emptying the nerve of acetylcholine. Botulinum toxin, tetanus toxin, β-bungarotoxin, Australian tiger snake venom (notexin), adenosine and GABA inhibit vesicle exocytosis and decrease MEPP frequency.
Quantitative proteomic analysis of venom from Southern India common krait (Bungarus caeruleus) and identification of poorly immunogenic toxins by immune-profiling against commercial antivenom
Published in Expert Review of Proteomics, 2019
Aparup Patra, Abhishek Chanda, Ashis K. Mukherjee
Indian cobra (Naja spp) venom has been shown to contain only post-synaptic neurotoxins [18,30]; however, the occurrence of both pre- and post-synaptic neurotoxins has been reported in Bungarus venom [14,15]. This variation may explain the different pathophysiologies seen in krait and cobra envenomation [54]. The β-bungarotoxin and κ-bungarotoxin (a subtype of 3FTx) representing pre-synaptic neurotoxin and post synaptic neurotoxin, respectively are present in krait venom [14,15]. The proteomic analysis revealed that SI B. caeruleus venom is comprised of a substantial amount of β-bungarotoxin (12.9%) and κ-BTx (5.24%) (Figure 2, Table 1). The β-bungarotoxin causes triphasic effects at the terminus – inhibition initially, a small spike of ACh release, then further inhibition of release. By depleting the ACh vesicles, activation causes the degeneration of the motor nerve terminal [55,56]. The effect of β-bungarotoxins on sphincter pupillae, levator palpebral superioris, neck muscles, bulbar muscles, the limbs, and finally, the diaphragm that leads to respiratory failure, are the primary symptoms of krait envenomation [53]. The κ-BTx affects the neuronal-type of nicotinic cholinoceptors (AChR) at the post-synaptic level in central cholinergic synapses in autonomic ganglia [57]. Because the damage caused by the pre-synaptic neurotoxin is irreversible, the neurological manifestation lasts for 2–3 weeks, as is observed in krait-envenomed patients [53].
Related Knowledge Centers
- Bungarotoxin
- Chemical Synapse
- Dendrotoxin
- Neurotoxin
- Phospholipase A2
- Snake Venom
- Kunitz Domain
- Acetylcholine
- Α-Bungarotoxin
- Κ-Bungarotoxin