Abstract:
:Snake venom kappa-neurotoxins are selective antagonists of nicotinic acetylcholine responses in avian, murine and bovine neurons, and have been used as probes for functionally defined vertebrate neuronal nicotinic receptors. The actions of kappa-bungarotoxin, a kappa-neurotoxin, have now been examined at a central invertebrate nicotinic receptor. kappa-Bungarotoxin is a potent antagonist (IC50 = 100 nM) of nicotinic responses, producing a long-lasting blockade of insect nicotinic acetylcholine receptors. The blockade appears to be competitive, and voltage-clamp experiments on an identified cockroach motorneuron indicate that the actions of kappa-bungarotoxin are not dependent on membrane potential. alpha-Bungarotoxin is also a potent antagonist at the cockroach central nicotinic receptor, and binds (Kd = 4.3 nM) to a nicotinic site in cockroach nervous tissue. kappa-Bungarotoxin recognizes this invertebrate nicotinic site with high affinity (Ki = 27 nM). A comparison of the pharmacological properties of insect nicotinic receptors with those of functionally defined receptors identified by kappa-neurotoxins in avian autonomic ganglia reveals several similarities. However, a striking exception is alpha-bungarotoxin, which is the most potent antagonist examined at cockroach nicotinic receptors, but fails to recognize functional autonomic ganglia nicotinic receptors even at very high concentrations. It is concluded that kappa-neurotoxins can be used as selective probes for neuronal nicotinic receptors in both vertebrates and invertebrates. Although invertebrates diverged from vertebrates over 600 million years ago, the results indicate that the neuronal nicotinic receptors found in species as diverse as cockroach and chick retain considerable structural similarity, and thus neuronal nicotinic receptors appear to be highly conserved membrane proteins.
journal_name
Brain Resjournal_title
Brain researchauthors
Pinnock RD,Lummis SC,Chiappinelli VA,Sattelle DBdoi
10.1016/0006-8993(88)90494-5subject
Has Abstractpub_date
1988-08-16 00:00:00pages
45-52issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(88)90494-5journal_volume
458pub_type
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